ChemWiki - User contributions [en]

It:Zithromycin

2006-12-08T22:17:34Z

Rx104: /* Dose */

=Zithromycin=

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! {{chembox header}} colspan="3" | Structure of Zithromycin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[image:zithromycin.bmp|200px|{{PAGENAME}}]]
|-
! {{chembox header}} align="center" colspan="3" |3D structure
|-
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title1
title2
HEADER NONAME 21-Nov-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 21-Nov-06 0 NONE 4
ATOM 1 C 0 0.648 -1.169 2.459 0.00 0.00 C+0
ATOM 2 C 0 -0.055 -0.745 1.242 0.00 0.00 C+0
ATOM 3 H 0 -1.003 -1.290 1.111 0.00 0.00 H+0
ATOM 4 C 0 -0.442 0.785 1.252 0.00 0.00 C+0
ATOM 5 H 0 -0.937 1.041 0.367 0.00 0.00 H+0
ATOM 6 O 0 0.757 1.554 1.427 0.00 0.00 O+0
ATOM 7 C 0 0.693 2.642 0.491 0.00 0.00 C+0
ATOM 8 H 0 -0.284 3.108 0.584 0.00 0.00 H+0
ATOM 9 C 0 1.791 3.647 0.836 0.00 0.00 C+0
ATOM 10 C 0 1.748 4.824 -0.136 0.00 0.00 C+0
ATOM 11 C 0 0.575 5.747 0.201 0.00 0.00 C+0
ATOM 12 O 0 2.964 5.582 0.024 0.00 0.00 O+0
ATOM 13 C 0 2.845 6.735 -0.812 0.00 0.00 C+0
ATOM 14 C 0 1.669 4.345 -1.580 0.00 0.00 C+0
ATOM 15 H 0 1.298 5.177 -2.202 0.00 0.00 H+0
ATOM 16 O 0 2.992 4.030 -2.042 0.00 0.00 O+0
ATOM 17 C 0 0.768 3.142 -1.793 0.00 0.00 C+0
ATOM 18 H 0 1.074 2.683 -2.763 0.00 0.00 H+0
ATOM 19 C 0 -0.691 3.562 -1.967 0.00 0.00 C+0
ATOM 20 O 0 0.903 2.134 -0.816 0.00 0.00 O+0
ATOM 21 C 0 -1.343 1.017 2.489 0.00 0.00 C+0
ATOM 22 H 0 -1.486 0.194 3.112 0.00 0.00 H+0
ATOM 23 C 0 -0.850 2.242 3.191 0.00 0.00 C+0
ATOM 24 C 0 -2.766 1.358 1.897 0.00 0.00 C+0
ATOM 25 C 0 -3.867 0.329 2.108 0.00 0.00 C+0
ATOM 26 C 0 -4.692 0.264 0.819 0.00 0.00 C+0
ATOM 27 H 0 -4.025 0.156 -0.061 0.00 0.00 H+0
ATOM 28 C 0 -5.445 1.602 0.636 0.00 0.00 C+0
ATOM 29 C 0 -6.154 1.607 -0.719 0.00 0.00 C+0
ATOM 30 C 0 -5.785 -0.826 0.828 0.00 0.00 C+0
ATOM 31 O 0 -6.993 -0.185 1.062 0.00 0.00 O+0
ATOM 32 C 0 -5.523 -1.749 2.106 0.00 0.00 C+0
ATOM 33 C 0 -5.778 -1.600 -0.464 0.00 0.00 C+0
ATOM 34 C 0 -4.669 -2.608 -0.625 0.00 0.00 C+0
ATOM 35 H 0 -3.902 -2.442 0.126 0.00 0.00 H+0
ATOM 36 C 0 -5.265 -4.052 -0.458 0.00 0.00 C+0
ATOM 37 N 0 -4.009 -2.649 -1.976 0.00 0.00 N+0
ATOM 38 C 0 -3.570 -1.215 -2.027 0.00 0.00 C+0
ATOM 39 C 0 -2.775 -3.328 -1.603 0.00 0.00 C+0
ATOM 40 C 0 -1.492 -2.913 -2.336 0.00 0.00 C+0
ATOM 41 H 0 -1.569 -2.024 -3.006 0.00 0.00 H+0
ATOM 42 C 0 -1.098 -4.084 -3.302 0.00 0.00 C+0
ATOM 43 C 0 -0.338 -2.695 -1.357 0.00 0.00 C+0
ATOM 44 C 0 0.063 -1.213 -1.254 0.00 0.00 C+0
ATOM 45 C 0 1.016 -0.946 -2.401 0.00 0.00 C+0
ATOM 46 O 0 -1.057 -0.335 -1.329 0.00 0.00 O+0
ATOM 47 C 0 0.863 -1.024 0.040 0.00 0.00 C+0
ATOM 48 H 0 1.516 -0.109 -0.133 0.00 0.00 H+0
ATOM 49 O 0 1.641 -2.161 0.353 0.00 0.00 O+0
ATOM 50 C 0 2.997 -1.718 0.453 0.00 0.00 C+0
ATOM 51 H 0 3.051 -0.868 1.132 0.00 0.00 H+0
ATOM 52 O 0 3.463 -1.326 -0.837 0.00 0.00 O+0
ATOM 53 C 0 4.746 -0.726 -0.667 0.00 0.00 C+0
ATOM 54 H 0 4.682 0.059 0.087 0.00 0.00 H+0
ATOM 55 C 0 5.203 -0.119 -1.995 0.00 0.00 C+0
ATOM 56 C 0 5.757 -1.783 -0.218 0.00 0.00 C+0
ATOM 57 C 0 5.309 -2.362 1.129 0.00 0.00 C+0
ATOM 58 H 0 5.361 -1.588 1.895 0.00 0.00 H+0
ATOM 59 N 0 6.185 -3.482 1.499 0.00 0.00 N+0
ATOM 60 C 0 6.245 -4.374 0.334 0.00 0.00 C+0
ATOM 61 C 0 7.532 -2.924 1.675 0.00 0.00 C+0
ATOM 62 C 0 3.865 -2.857 0.992 0.00 0.00 C+0
ATOM 63 H 0 3.832 -3.701 0.303 0.00 0.00 H+0
ATOM 64 O 0 3.377 -3.266 2.272 0.00 0.00 O+0
ATOM 65 O 0 -2.943 2.436 1.458 0.00 0.00 O+0
ATOM 66 H 0 -0.009 -1.046 3.320 0.00 0.00 H+0
ATOM 67 H 0 0.934 -2.217 2.367 0.00 0.00 H+0
ATOM 68 H 0 1.542 -0.559 2.593 0.00 0.00 H+0
ATOM 69 H 0 1.642 4.009 1.856 0.00 0.00 H+0
ATOM 70 H 0 2.765 3.156 0.776 0.00 0.00 H+0
ATOM 71 H 0 0.772 6.255 1.145 0.00 0.00 H+0
ATOM 72 H 0 0.454 6.485 -0.592 0.00 0.00 H+0
ATOM 73 H 0 -0.337 5.157 0.290 0.00 0.00 H+0
ATOM 74 H 0 3.784 7.288 -0.805 0.00 0.00 H+0
ATOM 75 H 0 2.615 6.423 -1.831 0.00 0.00 H+0
ATOM 76 H 0 2.045 7.373 -0.438 0.00 0.00 H+0
ATOM 77 H 0 2.905 3.731 -2.957 0.00 0.00 H+0
ATOM 78 H 0 -0.779 4.218 -2.834 0.00 0.00 H+0
ATOM 79 H 0 -1.308 2.676 -2.118 0.00 0.00 H+0
ATOM 80 H 0 -1.026 4.091 -1.075 0.00 0.00 H+0
ATOM 81 H 0 -0.936 3.101 2.526 0.00 0.00 H+0
ATOM 82 H 0 -1.449 2.414 4.086 0.00 0.00 H+0
ATOM 83 H 0 0.193 2.103 3.474 0.00 0.00 H+0
ATOM 84 H 0 -3.414 -0.608 2.297 0.00 0.00 H+0
ATOM 85 H 0 -4.512 0.647 2.995 0.00 0.00 H+0
ATOM 86 H 0 -6.181 1.717 1.432 0.00 0.00 H+0
ATOM 87 H 0 -4.734 2.428 0.677 0.00 0.00 H+0
ATOM 88 H 0 -6.594 2.589 -0.896 0.00 0.00 H+0
ATOM 89 H 0 -5.434 1.384 -1.507 0.00 0.00 H+0
ATOM 90 H 0 -6.940 0.852 -0.721 0.00 0.00 H+0
ATOM 91 H 0 -7.676 -0.870 1.067 0.00 0.00 H+0
ATOM 92 H 0 -5.580 -1.142 3.009 0.00 0.00 H+0
ATOM 93 H 0 -6.278 -2.534 2.147 0.00 0.00 H+0
ATOM 94 H 0 -4.533 -2.199 2.032 0.00 0.00 H+0
ATOM 95 H 0 -6.742 -2.171 -0.484 0.00 0.00 H+0
ATOM 96 H 0 -5.836 -0.955 -1.266 0.00 0.00 H+0
ATOM 97 H 0 -6.029 -4.220 -1.217 0.00 0.00 H+0
ATOM 98 H 0 -4.470 -4.789 -0.572 0.00 0.00 H+0
ATOM 99 H 0 -5.710 -4.149 0.533 0.00 0.00 H+0
ATOM 100 H 0 -3.026 -0.969 -1.115 0.00 0.00 H+0
ATOM 101 H 0 -2.920 -1.065 -2.889 0.00 0.00 H+0
ATOM 102 H 0 -4.444 -0.570 -2.115 0.00 0.00 H+0
ATOM 103 H 0 -2.546 -3.132 -0.486 0.00 0.00 H+0
ATOM 104 H 0 -2.915 -4.430 -1.755 0.00 0.00 H+0
ATOM 105 H 0 -1.905 -4.254 -4.015 0.00 0.00 H+0
ATOM 106 H 0 -0.188 -3.820 -3.840 0.00 0.00 H+0
ATOM 107 H 0 -0.928 -4.991 -2.723 0.00 0.00 H+0
ATOM 108 H 0 -0.699 -3.031 -0.383 0.00 0.00 H+0
ATOM 109 H 0 0.465 -3.306 -1.713 0.00 0.00 H+0
ATOM 110 H 0 0.480 -1.032 -3.347 0.00 0.00 H+0
ATOM 111 H 0 1.426 0.059 -2.306 0.00 0.00 H+0
ATOM 112 H 0 1.828 -1.673 -2.376 0.00 0.00 H+0
ATOM 113 H 0 -1.480 -0.493 -2.184 0.00 0.00 H+0
ATOM 114 H 0 4.486 0.638 -2.314 0.00 0.00 H+0
ATOM 115 H 0 6.183 0.340 -1.867 0.00 0.00 H+0
ATOM 116 H 0 5.264 -0.902 -2.751 0.00 0.00 H+0
ATOM 117 H 0 5.806 -2.580 -0.960 0.00 0.00 H+0
ATOM 118 H 0 6.740 -1.324 -0.109 0.00 0.00 H+0
ATOM 119 H 0 6.776 -5.287 0.603 0.00 0.00 H+0
ATOM 120 H 0 5.234 -4.623 0.014 0.00 0.00 H+0
ATOM 121 H 0 6.771 -3.874 -0.479 0.00 0.00 H+0
ATOM 122 H 0 7.491 -2.087 2.371 0.00 0.00 H+0
ATOM 123 H 0 8.196 -3.694 2.070 0.00 0.00 H+0
ATOM 124 H 0 7.910 -2.578 0.713 0.00 0.00 H+0
ATOM 125 H 0 2.468 -3.569 2.140 0.00 0.00 H+0
CONECT 1 2 66 67 68 NONE 130
CONECT 2 1 3 47 4 NONE 131
CONECT 4 2 5 6 21 NONE 132
CONECT 6 4 7 0 0 NONE 133
CONECT 7 6 8 20 9 NONE 134
CONECT 9 7 10 69 70 NONE 135
CONECT 10 9 11 12 14 NONE 136
CONECT 11 10 71 72 73 NONE 137
CONECT 12 10 13 0 0 NONE 138
CONECT 13 12 74 75 76 NONE 139
CONECT 14 10 15 16 17 NONE 140
CONECT 16 14 77 0 0 NONE 141
CONECT 17 14 18 19 20 NONE 142
CONECT 19 17 78 79 80 NONE 143
CONECT 20 17 7 0 0 NONE 144
CONECT 21 4 22 23 24 NONE 145
CONECT 23 21 81 82 83 NONE 146
CONECT 24 21 25 65 0 NONE 147
CONECT 25 24 26 84 85 NONE 148
CONECT 26 25 27 28 30 NONE 149
CONECT 28 26 29 86 87 NONE 150
CONECT 29 28 88 89 90 NONE 151
CONECT 30 26 31 32 33 NONE 152
CONECT 31 30 91 0 0 NONE 153
CONECT 32 30 92 93 94 NONE 154
CONECT 33 30 34 95 96 NONE 155
CONECT 34 33 35 36 37 NONE 156
CONECT 36 34 97 98 99 NONE 157
CONECT 37 34 38 39 0 NONE 158
CONECT 38 37 100 101 102 NONE 159
CONECT 39 37 40 103 104 NONE 160
CONECT 40 39 41 42 43 NONE 161
CONECT 42 40 105 106 107 NONE 162
CONECT 43 40 44 108 109 NONE 163
CONECT 44 43 45 46 47 NONE 164
CONECT 45 44 110 111 112 NONE 165
CONECT 46 44 113 0 0 NONE 166
CONECT 47 44 48 2 49 NONE 167
CONECT 49 47 50 0 0 NONE 168
CONECT 50 49 51 62 52 NONE 169
CONECT 52 50 53 0 0 NONE 170
CONECT 53 52 54 55 56 NONE 171
CONECT 55 53 114 115 116 NONE 172
CONECT 56 53 57 117 118 NONE 173
CONECT 57 56 58 59 62 NONE 174
CONECT 59 57 60 61 0 NONE 175
CONECT 60 59 119 120 121 NONE 176
CONECT 61 59 122 123 124 NONE 177
CONECT 62 57 63 50 64 NONE 178
CONECT 64 62 125 0 0 NONE 179
CONECT 65 24 0 0 0 NONE 180
END NONE 181

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|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|9-deoxy-9a-aza-9a-methyl-9a-<br> homoerythromycin A
|-
| colspan="1" |Other names
| colspan="2"|Azithromycin
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2"|83905-01-5
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2"|C<sub>38</sub>H<sub>72</sub>N<sub>2</sub>O<sub>12</sub>
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2"|C[C@H]1[C@H](O[C@H]3C[C@@]<br>(C)(OC)[C@@H](O)[C@H](C)O3)<br>[C@@H](C)C(C[C@H](CC)[C@](O)<br>(C)C[C@@H](C)N(C)C[C@H](C)<br>C[C@@](C)(O)[C@@H]1O[C@@H]2O<br>[C@H](C)C[C@H](N(C)C)[C@H]2O)=O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2"|748.98g/mol
|-
| colspan="1" |Appearance
| colspan="2"|Crystalline structure
|-
| colspan="1" |Melting point
| colspan="2"|136°C to 155°C
|-
|}

Confusingly, this popular anti-biotic is also known as azithromycin, and is marketed as zithromax by Pfizer. According to their website, it's the most widely sold antibiotic in the world. It is a member of a large class of antibiotics derived from erythromycin, which differs only from azithromycin in that the nitrogen in the macrocycle is replaced by a carbonyl group. They have similar activities with respect to bacteria and appear to work in much the same way, but azithromycin is much more readily accepted by the body, causing fewer and less severe side effects. This means that even though the drug itself is more expensive, the overall cost of its' use is lower as less follow up appointments are required.

==Mode of action==
Zithromycin is a macrolide antibiotic which works by interfering with bacterial protein synthesis by binding to the 50S subunit of the bacterial ribosome, thus inhibiting the translation of mRNA. This inhibits the growth of the bacteria, their ability to replicate and increase in numbers. This therefore stops the spread of infection and allows the body's immune system to kill any remaining bacteria.

In 1994 a [http://www.rsc.org/ejarchive/C3/1994/C39940001615.pdf joint study] conducted by Smithkline Beechams (now trading as GlaxoSmithKline) and the University of Manchester established using real time NMR spectroscopy and other more specialised methods that the drug molecule binds to the bacterial ribosomes in a two stage process, the first of which is the formation of a weak interaction between the ribosome and the amine in the macrocycle.

==Uses==
Zithromycin is a broad-spectrum antibiotic that is able to combat a variety of bacteria that cause a wide variety of bacterial infections namely:

*Chest or lower respiratory tract infections of the lungs and airways such as pneumonia and bronchitis.
* Upper respiratory tract infections of the nasal passages, sinuses and throat such as sinusitis, tonsillitis and pharyngitis.
*Bacterial infections of the middle ear such as otitis media
*Bacterial infections of the skin or soft tissue caused by [http://en.wikipedia.org/wiki/Staphylococcus_aureus| staphylococcus aureus]
*Sexually transmitted infections such as chlamydia

Zithromycin may not be used on people with allegic reactions to macrolide type antibiotics, eg erythromycin, or liver disease. The safety of zithromycin for use during pregnancy has not been established and as such is not recommended. Zithromycin can pass into breast milk and so is also not recommended for use by breast feeding mothers.

Azithromycin can also used to treat early Lyme disease, H. pylori infection, and other infections or to prevent heart infection in patients having dental or other procedures.

==Dose==
Zithromycin should be taken at least one hour before a meal or two hours after a meal to prevent it from binding to food and not being absorbed by the small intestine. Zithromycin should be taken once daily for a short course of five days for the majority of infections. Zithromycin is usually given as a double dose, 500mg, on the first day and as a single dose, 250mg once daily for the remaining four days and can be taken in tablet form or as an intravenous injection.

Missed dose:
Take the missed dose as soon as possiable unless it is almost the time for next dose. Do not take double dose at one time.

==Pharmacokinetics==
Zithromycin is acid stable and thus can be taken orally without the need to protect it from the gastric acids. Zithromycin is readily absorbed, and can diffuse into most tissues. Phagocytes in the body take up the zithromycin and actively transport the drug to the site of infection where it is actively released by phagocytosis. Thus large concentrations of zithromycin can be built up at the site of infection, with the concentration being up to 50 times higher in the tissue than in the plasma.

==Side effects==
*Disturbances of the gut such as diarrhoea, constipation, indigestion, nausea, vomiting or abdominal pain
*Headache
*Loss of appetite
*Dizziness
*Thrush infections
*Somnolence (sleepiness)
*Asthenia (weakness or loss of strength)
*Anxiety and agitation
*Hyperactivity
*Paraesthesia (pins and needles)
*Hearing distubances
*Palpitations (awareness of your heartbeat)
*Arrhythmias (abnormal heart beats)
*Arthralgia (pain in the joints)
*Decrease in the number of platelets or white blood cells in the blood
*Allergic skin reactions
*Photosensitivity (abnormal reaction of the skin to light, usually a rash)
*Convulsions (seizures)
*Liver or kidney disorders
*upset stomach
*stomach pain
*mild skin rash
*difficulty breathing or swallowing
*swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
*hoarseness
*yellowing of the skin or eyes
*rapid, pounding, or irregular heartbeat

==Synthesis==
A chemoselective methylation method for preparing zithromycin from 11-aza-10-deoxo-10-dihydroerythromycin and paraformaldehyde is as follows:

[[Image:Synthesis of azithromycin 2.GIF]]

==List of Reference Links==

http://www.sigmaaldrich.com/catalog/search/ProductDetail/FLUKA/75199 <br>
http://www.netdoctor.co.uk/medicines/100003113.html <br>
http://www.chemnetbase.com/scripts/docweb.exe?document+W3y8Rd2kVrC+2+44115#44115
http://en.wikipedia.org/wiki/Azithromycin
http://www.medicinenet.com/azithromycin/article.htm
http://www.rsc.org/ejarchive/C3/1994/C39940001615.pdf
http://www.chlamydiae.com/restricted/docs/labtests/treat_macrolides.asp

SciFinder - Rabinovich, I. M.; Pshenichnikov, V. G.; Kuz'min, I. A. (Otkrytoe Aktsionernoe Obshchestvo Aktsionernoe
Kurganskoe Obshchestvo Meditsinskikh Preparatov i Izdelii "Sintez", Russia). Russ. (2005)

http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a697037.html#if-i-forget

It:Zithromycin

2006-12-08T22:13:02Z

Rx104: /* List of Reference Links */

=Zithromycin=

{|class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" | Structure of Zithromycin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[image:zithromycin.bmp|200px|{{PAGENAME}}]]
|-
! {{chembox header}} align="center" colspan="3" |3D structure
|-
| align="center" colspan="3" bgcolor="#ffffff" |<jmol>
<jmolApplet>
<size>300</size>
<color>white</color>
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<inlineContents>water.mol
title1
title2
HEADER NONAME 21-Nov-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 21-Nov-06 0 NONE 4
ATOM 1 C 0 0.648 -1.169 2.459 0.00 0.00 C+0
ATOM 2 C 0 -0.055 -0.745 1.242 0.00 0.00 C+0
ATOM 3 H 0 -1.003 -1.290 1.111 0.00 0.00 H+0
ATOM 4 C 0 -0.442 0.785 1.252 0.00 0.00 C+0
ATOM 5 H 0 -0.937 1.041 0.367 0.00 0.00 H+0
ATOM 6 O 0 0.757 1.554 1.427 0.00 0.00 O+0
ATOM 7 C 0 0.693 2.642 0.491 0.00 0.00 C+0
ATOM 8 H 0 -0.284 3.108 0.584 0.00 0.00 H+0
ATOM 9 C 0 1.791 3.647 0.836 0.00 0.00 C+0
ATOM 10 C 0 1.748 4.824 -0.136 0.00 0.00 C+0
ATOM 11 C 0 0.575 5.747 0.201 0.00 0.00 C+0
ATOM 12 O 0 2.964 5.582 0.024 0.00 0.00 O+0
ATOM 13 C 0 2.845 6.735 -0.812 0.00 0.00 C+0
ATOM 14 C 0 1.669 4.345 -1.580 0.00 0.00 C+0
ATOM 15 H 0 1.298 5.177 -2.202 0.00 0.00 H+0
ATOM 16 O 0 2.992 4.030 -2.042 0.00 0.00 O+0
ATOM 17 C 0 0.768 3.142 -1.793 0.00 0.00 C+0
ATOM 18 H 0 1.074 2.683 -2.763 0.00 0.00 H+0
ATOM 19 C 0 -0.691 3.562 -1.967 0.00 0.00 C+0
ATOM 20 O 0 0.903 2.134 -0.816 0.00 0.00 O+0
ATOM 21 C 0 -1.343 1.017 2.489 0.00 0.00 C+0
ATOM 22 H 0 -1.486 0.194 3.112 0.00 0.00 H+0
ATOM 23 C 0 -0.850 2.242 3.191 0.00 0.00 C+0
ATOM 24 C 0 -2.766 1.358 1.897 0.00 0.00 C+0
ATOM 25 C 0 -3.867 0.329 2.108 0.00 0.00 C+0
ATOM 26 C 0 -4.692 0.264 0.819 0.00 0.00 C+0
ATOM 27 H 0 -4.025 0.156 -0.061 0.00 0.00 H+0
ATOM 28 C 0 -5.445 1.602 0.636 0.00 0.00 C+0
ATOM 29 C 0 -6.154 1.607 -0.719 0.00 0.00 C+0
ATOM 30 C 0 -5.785 -0.826 0.828 0.00 0.00 C+0
ATOM 31 O 0 -6.993 -0.185 1.062 0.00 0.00 O+0
ATOM 32 C 0 -5.523 -1.749 2.106 0.00 0.00 C+0
ATOM 33 C 0 -5.778 -1.600 -0.464 0.00 0.00 C+0
ATOM 34 C 0 -4.669 -2.608 -0.625 0.00 0.00 C+0
ATOM 35 H 0 -3.902 -2.442 0.126 0.00 0.00 H+0
ATOM 36 C 0 -5.265 -4.052 -0.458 0.00 0.00 C+0
ATOM 37 N 0 -4.009 -2.649 -1.976 0.00 0.00 N+0
ATOM 38 C 0 -3.570 -1.215 -2.027 0.00 0.00 C+0
ATOM 39 C 0 -2.775 -3.328 -1.603 0.00 0.00 C+0
ATOM 40 C 0 -1.492 -2.913 -2.336 0.00 0.00 C+0
ATOM 41 H 0 -1.569 -2.024 -3.006 0.00 0.00 H+0
ATOM 42 C 0 -1.098 -4.084 -3.302 0.00 0.00 C+0
ATOM 43 C 0 -0.338 -2.695 -1.357 0.00 0.00 C+0
ATOM 44 C 0 0.063 -1.213 -1.254 0.00 0.00 C+0
ATOM 45 C 0 1.016 -0.946 -2.401 0.00 0.00 C+0
ATOM 46 O 0 -1.057 -0.335 -1.329 0.00 0.00 O+0
ATOM 47 C 0 0.863 -1.024 0.040 0.00 0.00 C+0
ATOM 48 H 0 1.516 -0.109 -0.133 0.00 0.00 H+0
ATOM 49 O 0 1.641 -2.161 0.353 0.00 0.00 O+0
ATOM 50 C 0 2.997 -1.718 0.453 0.00 0.00 C+0
ATOM 51 H 0 3.051 -0.868 1.132 0.00 0.00 H+0
ATOM 52 O 0 3.463 -1.326 -0.837 0.00 0.00 O+0
ATOM 53 C 0 4.746 -0.726 -0.667 0.00 0.00 C+0
ATOM 54 H 0 4.682 0.059 0.087 0.00 0.00 H+0
ATOM 55 C 0 5.203 -0.119 -1.995 0.00 0.00 C+0
ATOM 56 C 0 5.757 -1.783 -0.218 0.00 0.00 C+0
ATOM 57 C 0 5.309 -2.362 1.129 0.00 0.00 C+0
ATOM 58 H 0 5.361 -1.588 1.895 0.00 0.00 H+0
ATOM 59 N 0 6.185 -3.482 1.499 0.00 0.00 N+0
ATOM 60 C 0 6.245 -4.374 0.334 0.00 0.00 C+0
ATOM 61 C 0 7.532 -2.924 1.675 0.00 0.00 C+0
ATOM 62 C 0 3.865 -2.857 0.992 0.00 0.00 C+0
ATOM 63 H 0 3.832 -3.701 0.303 0.00 0.00 H+0
ATOM 64 O 0 3.377 -3.266 2.272 0.00 0.00 O+0
ATOM 65 O 0 -2.943 2.436 1.458 0.00 0.00 O+0
ATOM 66 H 0 -0.009 -1.046 3.320 0.00 0.00 H+0
ATOM 67 H 0 0.934 -2.217 2.367 0.00 0.00 H+0
ATOM 68 H 0 1.542 -0.559 2.593 0.00 0.00 H+0
ATOM 69 H 0 1.642 4.009 1.856 0.00 0.00 H+0
ATOM 70 H 0 2.765 3.156 0.776 0.00 0.00 H+0
ATOM 71 H 0 0.772 6.255 1.145 0.00 0.00 H+0
ATOM 72 H 0 0.454 6.485 -0.592 0.00 0.00 H+0
ATOM 73 H 0 -0.337 5.157 0.290 0.00 0.00 H+0
ATOM 74 H 0 3.784 7.288 -0.805 0.00 0.00 H+0
ATOM 75 H 0 2.615 6.423 -1.831 0.00 0.00 H+0
ATOM 76 H 0 2.045 7.373 -0.438 0.00 0.00 H+0
ATOM 77 H 0 2.905 3.731 -2.957 0.00 0.00 H+0
ATOM 78 H 0 -0.779 4.218 -2.834 0.00 0.00 H+0
ATOM 79 H 0 -1.308 2.676 -2.118 0.00 0.00 H+0
ATOM 80 H 0 -1.026 4.091 -1.075 0.00 0.00 H+0
ATOM 81 H 0 -0.936 3.101 2.526 0.00 0.00 H+0
ATOM 82 H 0 -1.449 2.414 4.086 0.00 0.00 H+0
ATOM 83 H 0 0.193 2.103 3.474 0.00 0.00 H+0
ATOM 84 H 0 -3.414 -0.608 2.297 0.00 0.00 H+0
ATOM 85 H 0 -4.512 0.647 2.995 0.00 0.00 H+0
ATOM 86 H 0 -6.181 1.717 1.432 0.00 0.00 H+0
ATOM 87 H 0 -4.734 2.428 0.677 0.00 0.00 H+0
ATOM 88 H 0 -6.594 2.589 -0.896 0.00 0.00 H+0
ATOM 89 H 0 -5.434 1.384 -1.507 0.00 0.00 H+0
ATOM 90 H 0 -6.940 0.852 -0.721 0.00 0.00 H+0
ATOM 91 H 0 -7.676 -0.870 1.067 0.00 0.00 H+0
ATOM 92 H 0 -5.580 -1.142 3.009 0.00 0.00 H+0
ATOM 93 H 0 -6.278 -2.534 2.147 0.00 0.00 H+0
ATOM 94 H 0 -4.533 -2.199 2.032 0.00 0.00 H+0
ATOM 95 H 0 -6.742 -2.171 -0.484 0.00 0.00 H+0
ATOM 96 H 0 -5.836 -0.955 -1.266 0.00 0.00 H+0
ATOM 97 H 0 -6.029 -4.220 -1.217 0.00 0.00 H+0
ATOM 98 H 0 -4.470 -4.789 -0.572 0.00 0.00 H+0
ATOM 99 H 0 -5.710 -4.149 0.533 0.00 0.00 H+0
ATOM 100 H 0 -3.026 -0.969 -1.115 0.00 0.00 H+0
ATOM 101 H 0 -2.920 -1.065 -2.889 0.00 0.00 H+0
ATOM 102 H 0 -4.444 -0.570 -2.115 0.00 0.00 H+0
ATOM 103 H 0 -2.546 -3.132 -0.486 0.00 0.00 H+0
ATOM 104 H 0 -2.915 -4.430 -1.755 0.00 0.00 H+0
ATOM 105 H 0 -1.905 -4.254 -4.015 0.00 0.00 H+0
ATOM 106 H 0 -0.188 -3.820 -3.840 0.00 0.00 H+0
ATOM 107 H 0 -0.928 -4.991 -2.723 0.00 0.00 H+0
ATOM 108 H 0 -0.699 -3.031 -0.383 0.00 0.00 H+0
ATOM 109 H 0 0.465 -3.306 -1.713 0.00 0.00 H+0
ATOM 110 H 0 0.480 -1.032 -3.347 0.00 0.00 H+0
ATOM 111 H 0 1.426 0.059 -2.306 0.00 0.00 H+0
ATOM 112 H 0 1.828 -1.673 -2.376 0.00 0.00 H+0
ATOM 113 H 0 -1.480 -0.493 -2.184 0.00 0.00 H+0
ATOM 114 H 0 4.486 0.638 -2.314 0.00 0.00 H+0
ATOM 115 H 0 6.183 0.340 -1.867 0.00 0.00 H+0
ATOM 116 H 0 5.264 -0.902 -2.751 0.00 0.00 H+0
ATOM 117 H 0 5.806 -2.580 -0.960 0.00 0.00 H+0
ATOM 118 H 0 6.740 -1.324 -0.109 0.00 0.00 H+0
ATOM 119 H 0 6.776 -5.287 0.603 0.00 0.00 H+0
ATOM 120 H 0 5.234 -4.623 0.014 0.00 0.00 H+0
ATOM 121 H 0 6.771 -3.874 -0.479 0.00 0.00 H+0
ATOM 122 H 0 7.491 -2.087 2.371 0.00 0.00 H+0
ATOM 123 H 0 8.196 -3.694 2.070 0.00 0.00 H+0
ATOM 124 H 0 7.910 -2.578 0.713 0.00 0.00 H+0
ATOM 125 H 0 2.468 -3.569 2.140 0.00 0.00 H+0
CONECT 1 2 66 67 68 NONE 130
CONECT 2 1 3 47 4 NONE 131
CONECT 4 2 5 6 21 NONE 132
CONECT 6 4 7 0 0 NONE 133
CONECT 7 6 8 20 9 NONE 134
CONECT 9 7 10 69 70 NONE 135
CONECT 10 9 11 12 14 NONE 136
CONECT 11 10 71 72 73 NONE 137
CONECT 12 10 13 0 0 NONE 138
CONECT 13 12 74 75 76 NONE 139
CONECT 14 10 15 16 17 NONE 140
CONECT 16 14 77 0 0 NONE 141
CONECT 17 14 18 19 20 NONE 142
CONECT 19 17 78 79 80 NONE 143
CONECT 20 17 7 0 0 NONE 144
CONECT 21 4 22 23 24 NONE 145
CONECT 23 21 81 82 83 NONE 146
CONECT 24 21 25 65 0 NONE 147
CONECT 25 24 26 84 85 NONE 148
CONECT 26 25 27 28 30 NONE 149
CONECT 28 26 29 86 87 NONE 150
CONECT 29 28 88 89 90 NONE 151
CONECT 30 26 31 32 33 NONE 152
CONECT 31 30 91 0 0 NONE 153
CONECT 32 30 92 93 94 NONE 154
CONECT 33 30 34 95 96 NONE 155
CONECT 34 33 35 36 37 NONE 156
CONECT 36 34 97 98 99 NONE 157
CONECT 37 34 38 39 0 NONE 158
CONECT 38 37 100 101 102 NONE 159
CONECT 39 37 40 103 104 NONE 160
CONECT 40 39 41 42 43 NONE 161
CONECT 42 40 105 106 107 NONE 162
CONECT 43 40 44 108 109 NONE 163
CONECT 44 43 45 46 47 NONE 164
CONECT 45 44 110 111 112 NONE 165
CONECT 46 44 113 0 0 NONE 166
CONECT 47 44 48 2 49 NONE 167
CONECT 49 47 50 0 0 NONE 168
CONECT 50 49 51 62 52 NONE 169
CONECT 52 50 53 0 0 NONE 170
CONECT 53 52 54 55 56 NONE 171
CONECT 55 53 114 115 116 NONE 172
CONECT 56 53 57 117 118 NONE 173
CONECT 57 56 58 59 62 NONE 174
CONECT 59 57 60 61 0 NONE 175
CONECT 60 59 119 120 121 NONE 176
CONECT 61 59 122 123 124 NONE 177
CONECT 62 57 63 50 64 NONE 178
CONECT 64 62 125 0 0 NONE 179
CONECT 65 24 0 0 0 NONE 180
END NONE 181

M END</inlineContents>
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|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|9-deoxy-9a-aza-9a-methyl-9a-<br> homoerythromycin A
|-
| colspan="1" |Other names
| colspan="2"|Azithromycin
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2"|83905-01-5
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2"|C<sub>38</sub>H<sub>72</sub>N<sub>2</sub>O<sub>12</sub>
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2"|C[C@H]1[C@H](O[C@H]3C[C@@]<br>(C)(OC)[C@@H](O)[C@H](C)O3)<br>[C@@H](C)C(C[C@H](CC)[C@](O)<br>(C)C[C@@H](C)N(C)C[C@H](C)<br>C[C@@](C)(O)[C@@H]1O[C@@H]2O<br>[C@H](C)C[C@H](N(C)C)[C@H]2O)=O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2"|748.98g/mol
|-
| colspan="1" |Appearance
| colspan="2"|Crystalline structure
|-
| colspan="1" |Melting point
| colspan="2"|136°C to 155°C
|-
|}

Confusingly, this popular anti-biotic is also known as azithromycin, and is marketed as zithromax by Pfizer. According to their website, it's the most widely sold antibiotic in the world. It is a member of a large class of antibiotics derived from erythromycin, which differs only from azithromycin in that the nitrogen in the macrocycle is replaced by a carbonyl group. They have similar activities with respect to bacteria and appear to work in much the same way, but azithromycin is much more readily accepted by the body, causing fewer and less severe side effects. This means that even though the drug itself is more expensive, the overall cost of its' use is lower as less follow up appointments are required.

==Mode of action==
Zithromycin is a macrolide antibiotic which works by interfering with bacterial protein synthesis by binding to the 50S subunit of the bacterial ribosome, thus inhibiting the translation of mRNA. This inhibits the growth of the bacteria, their ability to replicate and increase in numbers. This therefore stops the spread of infection and allows the body's immune system to kill any remaining bacteria.

In 1994 a [http://www.rsc.org/ejarchive/C3/1994/C39940001615.pdf joint study] conducted by Smithkline Beechams (now trading as GlaxoSmithKline) and the University of Manchester established using real time NMR spectroscopy and other more specialised methods that the drug molecule binds to the bacterial ribosomes in a two stage process, the first of which is the formation of a weak interaction between the ribosome and the amine in the macrocycle.

==Uses==
Zithromycin is a broad-spectrum antibiotic that is able to combat a variety of bacteria that cause a wide variety of bacterial infections namely:

*Chest or lower respiratory tract infections of the lungs and airways such as pneumonia and bronchitis.
* Upper respiratory tract infections of the nasal passages, sinuses and throat such as sinusitis, tonsillitis and pharyngitis.
*Bacterial infections of the middle ear such as otitis media
*Bacterial infections of the skin or soft tissue caused by [http://en.wikipedia.org/wiki/Staphylococcus_aureus| staphylococcus aureus]
*Sexually transmitted infections such as chlamydia

Zithromycin may not be used on people with allegic reactions to macrolide type antibiotics, eg erythromycin, or liver disease. The safety of zithromycin for use during pregnancy has not been established and as such is not recommended. Zithromycin can pass into breast milk and so is also not recommended for use by breast feeding mothers.

Azithromycin can also used to treat early Lyme disease, H. pylori infection, and other infections or to prevent heart infection in patients having dental or other procedures.

==Dose==
Zithromycin should be taken at least one hour before a meal or two hours after a meal to prevent it from binding to food and not being absorbed by the small intestine. Zithromycin should be taken once daily for a short course of five days for the majority of infections. Zithromycin is usually given as a double dose, 500mg, on the first day and as a single dose, 250mg once daily for the remaining four days and can be taken in tablet form or as an intravenous injection.

==Pharmacokinetics==
Zithromycin is acid stable and thus can be taken orally without the need to protect it from the gastric acids. Zithromycin is readily absorbed, and can diffuse into most tissues. Phagocytes in the body take up the zithromycin and actively transport the drug to the site of infection where it is actively released by phagocytosis. Thus large concentrations of zithromycin can be built up at the site of infection, with the concentration being up to 50 times higher in the tissue than in the plasma.

==Side effects==
*Disturbances of the gut such as diarrhoea, constipation, indigestion, nausea, vomiting or abdominal pain
*Headache
*Loss of appetite
*Dizziness
*Thrush infections
*Somnolence (sleepiness)
*Asthenia (weakness or loss of strength)
*Anxiety and agitation
*Hyperactivity
*Paraesthesia (pins and needles)
*Hearing distubances
*Palpitations (awareness of your heartbeat)
*Arrhythmias (abnormal heart beats)
*Arthralgia (pain in the joints)
*Decrease in the number of platelets or white blood cells in the blood
*Allergic skin reactions
*Photosensitivity (abnormal reaction of the skin to light, usually a rash)
*Convulsions (seizures)
*Liver or kidney disorders
*upset stomach
*stomach pain
*mild skin rash
*difficulty breathing or swallowing
*swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
*hoarseness
*yellowing of the skin or eyes
*rapid, pounding, or irregular heartbeat

==Synthesis==
A chemoselective methylation method for preparing zithromycin from 11-aza-10-deoxo-10-dihydroerythromycin and paraformaldehyde is as follows:

[[Image:Synthesis of azithromycin 2.GIF]]

==List of Reference Links==

http://www.sigmaaldrich.com/catalog/search/ProductDetail/FLUKA/75199 <br>
http://www.netdoctor.co.uk/medicines/100003113.html <br>
http://www.chemnetbase.com/scripts/docweb.exe?document+W3y8Rd2kVrC+2+44115#44115
http://en.wikipedia.org/wiki/Azithromycin
http://www.medicinenet.com/azithromycin/article.htm
http://www.rsc.org/ejarchive/C3/1994/C39940001615.pdf
http://www.chlamydiae.com/restricted/docs/labtests/treat_macrolides.asp

SciFinder - Rabinovich, I. M.; Pshenichnikov, V. G.; Kuz'min, I. A. (Otkrytoe Aktsionernoe Obshchestvo Aktsionernoe
Kurganskoe Obshchestvo Meditsinskikh Preparatov i Izdelii "Sintez", Russia). Russ. (2005)

http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a697037.html#if-i-forget

It:Zithromycin

2006-12-08T22:12:47Z

Rx104: /* List of Reference Links */

=Zithromycin=

{|class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" | Structure of Zithromycin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[image:zithromycin.bmp|200px|{{PAGENAME}}]]
|-
! {{chembox header}} align="center" colspan="3" |3D structure
|-
| align="center" colspan="3" bgcolor="#ffffff" |<jmol>
<jmolApplet>
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<color>white</color>
<script>zoom 80; bns on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
title1
title2
HEADER NONAME 21-Nov-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 21-Nov-06 0 NONE 4
ATOM 1 C 0 0.648 -1.169 2.459 0.00 0.00 C+0
ATOM 2 C 0 -0.055 -0.745 1.242 0.00 0.00 C+0
ATOM 3 H 0 -1.003 -1.290 1.111 0.00 0.00 H+0
ATOM 4 C 0 -0.442 0.785 1.252 0.00 0.00 C+0
ATOM 5 H 0 -0.937 1.041 0.367 0.00 0.00 H+0
ATOM 6 O 0 0.757 1.554 1.427 0.00 0.00 O+0
ATOM 7 C 0 0.693 2.642 0.491 0.00 0.00 C+0
ATOM 8 H 0 -0.284 3.108 0.584 0.00 0.00 H+0
ATOM 9 C 0 1.791 3.647 0.836 0.00 0.00 C+0
ATOM 10 C 0 1.748 4.824 -0.136 0.00 0.00 C+0
ATOM 11 C 0 0.575 5.747 0.201 0.00 0.00 C+0
ATOM 12 O 0 2.964 5.582 0.024 0.00 0.00 O+0
ATOM 13 C 0 2.845 6.735 -0.812 0.00 0.00 C+0
ATOM 14 C 0 1.669 4.345 -1.580 0.00 0.00 C+0
ATOM 15 H 0 1.298 5.177 -2.202 0.00 0.00 H+0
ATOM 16 O 0 2.992 4.030 -2.042 0.00 0.00 O+0
ATOM 17 C 0 0.768 3.142 -1.793 0.00 0.00 C+0
ATOM 18 H 0 1.074 2.683 -2.763 0.00 0.00 H+0
ATOM 19 C 0 -0.691 3.562 -1.967 0.00 0.00 C+0
ATOM 20 O 0 0.903 2.134 -0.816 0.00 0.00 O+0
ATOM 21 C 0 -1.343 1.017 2.489 0.00 0.00 C+0
ATOM 22 H 0 -1.486 0.194 3.112 0.00 0.00 H+0
ATOM 23 C 0 -0.850 2.242 3.191 0.00 0.00 C+0
ATOM 24 C 0 -2.766 1.358 1.897 0.00 0.00 C+0
ATOM 25 C 0 -3.867 0.329 2.108 0.00 0.00 C+0
ATOM 26 C 0 -4.692 0.264 0.819 0.00 0.00 C+0
ATOM 27 H 0 -4.025 0.156 -0.061 0.00 0.00 H+0
ATOM 28 C 0 -5.445 1.602 0.636 0.00 0.00 C+0
ATOM 29 C 0 -6.154 1.607 -0.719 0.00 0.00 C+0
ATOM 30 C 0 -5.785 -0.826 0.828 0.00 0.00 C+0
ATOM 31 O 0 -6.993 -0.185 1.062 0.00 0.00 O+0
ATOM 32 C 0 -5.523 -1.749 2.106 0.00 0.00 C+0
ATOM 33 C 0 -5.778 -1.600 -0.464 0.00 0.00 C+0
ATOM 34 C 0 -4.669 -2.608 -0.625 0.00 0.00 C+0
ATOM 35 H 0 -3.902 -2.442 0.126 0.00 0.00 H+0
ATOM 36 C 0 -5.265 -4.052 -0.458 0.00 0.00 C+0
ATOM 37 N 0 -4.009 -2.649 -1.976 0.00 0.00 N+0
ATOM 38 C 0 -3.570 -1.215 -2.027 0.00 0.00 C+0
ATOM 39 C 0 -2.775 -3.328 -1.603 0.00 0.00 C+0
ATOM 40 C 0 -1.492 -2.913 -2.336 0.00 0.00 C+0
ATOM 41 H 0 -1.569 -2.024 -3.006 0.00 0.00 H+0
ATOM 42 C 0 -1.098 -4.084 -3.302 0.00 0.00 C+0
ATOM 43 C 0 -0.338 -2.695 -1.357 0.00 0.00 C+0
ATOM 44 C 0 0.063 -1.213 -1.254 0.00 0.00 C+0
ATOM 45 C 0 1.016 -0.946 -2.401 0.00 0.00 C+0
ATOM 46 O 0 -1.057 -0.335 -1.329 0.00 0.00 O+0
ATOM 47 C 0 0.863 -1.024 0.040 0.00 0.00 C+0
ATOM 48 H 0 1.516 -0.109 -0.133 0.00 0.00 H+0
ATOM 49 O 0 1.641 -2.161 0.353 0.00 0.00 O+0
ATOM 50 C 0 2.997 -1.718 0.453 0.00 0.00 C+0
ATOM 51 H 0 3.051 -0.868 1.132 0.00 0.00 H+0
ATOM 52 O 0 3.463 -1.326 -0.837 0.00 0.00 O+0
ATOM 53 C 0 4.746 -0.726 -0.667 0.00 0.00 C+0
ATOM 54 H 0 4.682 0.059 0.087 0.00 0.00 H+0
ATOM 55 C 0 5.203 -0.119 -1.995 0.00 0.00 C+0
ATOM 56 C 0 5.757 -1.783 -0.218 0.00 0.00 C+0
ATOM 57 C 0 5.309 -2.362 1.129 0.00 0.00 C+0
ATOM 58 H 0 5.361 -1.588 1.895 0.00 0.00 H+0
ATOM 59 N 0 6.185 -3.482 1.499 0.00 0.00 N+0
ATOM 60 C 0 6.245 -4.374 0.334 0.00 0.00 C+0
ATOM 61 C 0 7.532 -2.924 1.675 0.00 0.00 C+0
ATOM 62 C 0 3.865 -2.857 0.992 0.00 0.00 C+0
ATOM 63 H 0 3.832 -3.701 0.303 0.00 0.00 H+0
ATOM 64 O 0 3.377 -3.266 2.272 0.00 0.00 O+0
ATOM 65 O 0 -2.943 2.436 1.458 0.00 0.00 O+0
ATOM 66 H 0 -0.009 -1.046 3.320 0.00 0.00 H+0
ATOM 67 H 0 0.934 -2.217 2.367 0.00 0.00 H+0
ATOM 68 H 0 1.542 -0.559 2.593 0.00 0.00 H+0
ATOM 69 H 0 1.642 4.009 1.856 0.00 0.00 H+0
ATOM 70 H 0 2.765 3.156 0.776 0.00 0.00 H+0
ATOM 71 H 0 0.772 6.255 1.145 0.00 0.00 H+0
ATOM 72 H 0 0.454 6.485 -0.592 0.00 0.00 H+0
ATOM 73 H 0 -0.337 5.157 0.290 0.00 0.00 H+0
ATOM 74 H 0 3.784 7.288 -0.805 0.00 0.00 H+0
ATOM 75 H 0 2.615 6.423 -1.831 0.00 0.00 H+0
ATOM 76 H 0 2.045 7.373 -0.438 0.00 0.00 H+0
ATOM 77 H 0 2.905 3.731 -2.957 0.00 0.00 H+0
ATOM 78 H 0 -0.779 4.218 -2.834 0.00 0.00 H+0
ATOM 79 H 0 -1.308 2.676 -2.118 0.00 0.00 H+0
ATOM 80 H 0 -1.026 4.091 -1.075 0.00 0.00 H+0
ATOM 81 H 0 -0.936 3.101 2.526 0.00 0.00 H+0
ATOM 82 H 0 -1.449 2.414 4.086 0.00 0.00 H+0
ATOM 83 H 0 0.193 2.103 3.474 0.00 0.00 H+0
ATOM 84 H 0 -3.414 -0.608 2.297 0.00 0.00 H+0
ATOM 85 H 0 -4.512 0.647 2.995 0.00 0.00 H+0
ATOM 86 H 0 -6.181 1.717 1.432 0.00 0.00 H+0
ATOM 87 H 0 -4.734 2.428 0.677 0.00 0.00 H+0
ATOM 88 H 0 -6.594 2.589 -0.896 0.00 0.00 H+0
ATOM 89 H 0 -5.434 1.384 -1.507 0.00 0.00 H+0
ATOM 90 H 0 -6.940 0.852 -0.721 0.00 0.00 H+0
ATOM 91 H 0 -7.676 -0.870 1.067 0.00 0.00 H+0
ATOM 92 H 0 -5.580 -1.142 3.009 0.00 0.00 H+0
ATOM 93 H 0 -6.278 -2.534 2.147 0.00 0.00 H+0
ATOM 94 H 0 -4.533 -2.199 2.032 0.00 0.00 H+0
ATOM 95 H 0 -6.742 -2.171 -0.484 0.00 0.00 H+0
ATOM 96 H 0 -5.836 -0.955 -1.266 0.00 0.00 H+0
ATOM 97 H 0 -6.029 -4.220 -1.217 0.00 0.00 H+0
ATOM 98 H 0 -4.470 -4.789 -0.572 0.00 0.00 H+0
ATOM 99 H 0 -5.710 -4.149 0.533 0.00 0.00 H+0
ATOM 100 H 0 -3.026 -0.969 -1.115 0.00 0.00 H+0
ATOM 101 H 0 -2.920 -1.065 -2.889 0.00 0.00 H+0
ATOM 102 H 0 -4.444 -0.570 -2.115 0.00 0.00 H+0
ATOM 103 H 0 -2.546 -3.132 -0.486 0.00 0.00 H+0
ATOM 104 H 0 -2.915 -4.430 -1.755 0.00 0.00 H+0
ATOM 105 H 0 -1.905 -4.254 -4.015 0.00 0.00 H+0
ATOM 106 H 0 -0.188 -3.820 -3.840 0.00 0.00 H+0
ATOM 107 H 0 -0.928 -4.991 -2.723 0.00 0.00 H+0
ATOM 108 H 0 -0.699 -3.031 -0.383 0.00 0.00 H+0
ATOM 109 H 0 0.465 -3.306 -1.713 0.00 0.00 H+0
ATOM 110 H 0 0.480 -1.032 -3.347 0.00 0.00 H+0
ATOM 111 H 0 1.426 0.059 -2.306 0.00 0.00 H+0
ATOM 112 H 0 1.828 -1.673 -2.376 0.00 0.00 H+0
ATOM 113 H 0 -1.480 -0.493 -2.184 0.00 0.00 H+0
ATOM 114 H 0 4.486 0.638 -2.314 0.00 0.00 H+0
ATOM 115 H 0 6.183 0.340 -1.867 0.00 0.00 H+0
ATOM 116 H 0 5.264 -0.902 -2.751 0.00 0.00 H+0
ATOM 117 H 0 5.806 -2.580 -0.960 0.00 0.00 H+0
ATOM 118 H 0 6.740 -1.324 -0.109 0.00 0.00 H+0
ATOM 119 H 0 6.776 -5.287 0.603 0.00 0.00 H+0
ATOM 120 H 0 5.234 -4.623 0.014 0.00 0.00 H+0
ATOM 121 H 0 6.771 -3.874 -0.479 0.00 0.00 H+0
ATOM 122 H 0 7.491 -2.087 2.371 0.00 0.00 H+0
ATOM 123 H 0 8.196 -3.694 2.070 0.00 0.00 H+0
ATOM 124 H 0 7.910 -2.578 0.713 0.00 0.00 H+0
ATOM 125 H 0 2.468 -3.569 2.140 0.00 0.00 H+0
CONECT 1 2 66 67 68 NONE 130
CONECT 2 1 3 47 4 NONE 131
CONECT 4 2 5 6 21 NONE 132
CONECT 6 4 7 0 0 NONE 133
CONECT 7 6 8 20 9 NONE 134
CONECT 9 7 10 69 70 NONE 135
CONECT 10 9 11 12 14 NONE 136
CONECT 11 10 71 72 73 NONE 137
CONECT 12 10 13 0 0 NONE 138
CONECT 13 12 74 75 76 NONE 139
CONECT 14 10 15 16 17 NONE 140
CONECT 16 14 77 0 0 NONE 141
CONECT 17 14 18 19 20 NONE 142
CONECT 19 17 78 79 80 NONE 143
CONECT 20 17 7 0 0 NONE 144
CONECT 21 4 22 23 24 NONE 145
CONECT 23 21 81 82 83 NONE 146
CONECT 24 21 25 65 0 NONE 147
CONECT 25 24 26 84 85 NONE 148
CONECT 26 25 27 28 30 NONE 149
CONECT 28 26 29 86 87 NONE 150
CONECT 29 28 88 89 90 NONE 151
CONECT 30 26 31 32 33 NONE 152
CONECT 31 30 91 0 0 NONE 153
CONECT 32 30 92 93 94 NONE 154
CONECT 33 30 34 95 96 NONE 155
CONECT 34 33 35 36 37 NONE 156
CONECT 36 34 97 98 99 NONE 157
CONECT 37 34 38 39 0 NONE 158
CONECT 38 37 100 101 102 NONE 159
CONECT 39 37 40 103 104 NONE 160
CONECT 40 39 41 42 43 NONE 161
CONECT 42 40 105 106 107 NONE 162
CONECT 43 40 44 108 109 NONE 163
CONECT 44 43 45 46 47 NONE 164
CONECT 45 44 110 111 112 NONE 165
CONECT 46 44 113 0 0 NONE 166
CONECT 47 44 48 2 49 NONE 167
CONECT 49 47 50 0 0 NONE 168
CONECT 50 49 51 62 52 NONE 169
CONECT 52 50 53 0 0 NONE 170
CONECT 53 52 54 55 56 NONE 171
CONECT 55 53 114 115 116 NONE 172
CONECT 56 53 57 117 118 NONE 173
CONECT 57 56 58 59 62 NONE 174
CONECT 59 57 60 61 0 NONE 175
CONECT 60 59 119 120 121 NONE 176
CONECT 61 59 122 123 124 NONE 177
CONECT 62 57 63 50 64 NONE 178
CONECT 64 62 125 0 0 NONE 179
CONECT 65 24 0 0 0 NONE 180
END NONE 181

M END</inlineContents>
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|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|9-deoxy-9a-aza-9a-methyl-9a-<br> homoerythromycin A
|-
| colspan="1" |Other names
| colspan="2"|Azithromycin
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2"|83905-01-5
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2"|C<sub>38</sub>H<sub>72</sub>N<sub>2</sub>O<sub>12</sub>
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2"|C[C@H]1[C@H](O[C@H]3C[C@@]<br>(C)(OC)[C@@H](O)[C@H](C)O3)<br>[C@@H](C)C(C[C@H](CC)[C@](O)<br>(C)C[C@@H](C)N(C)C[C@H](C)<br>C[C@@](C)(O)[C@@H]1O[C@@H]2O<br>[C@H](C)C[C@H](N(C)C)[C@H]2O)=O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2"|748.98g/mol
|-
| colspan="1" |Appearance
| colspan="2"|Crystalline structure
|-
| colspan="1" |Melting point
| colspan="2"|136°C to 155°C
|-
|}

Confusingly, this popular anti-biotic is also known as azithromycin, and is marketed as zithromax by Pfizer. According to their website, it's the most widely sold antibiotic in the world. It is a member of a large class of antibiotics derived from erythromycin, which differs only from azithromycin in that the nitrogen in the macrocycle is replaced by a carbonyl group. They have similar activities with respect to bacteria and appear to work in much the same way, but azithromycin is much more readily accepted by the body, causing fewer and less severe side effects. This means that even though the drug itself is more expensive, the overall cost of its' use is lower as less follow up appointments are required.

==Mode of action==
Zithromycin is a macrolide antibiotic which works by interfering with bacterial protein synthesis by binding to the 50S subunit of the bacterial ribosome, thus inhibiting the translation of mRNA. This inhibits the growth of the bacteria, their ability to replicate and increase in numbers. This therefore stops the spread of infection and allows the body's immune system to kill any remaining bacteria.

In 1994 a [http://www.rsc.org/ejarchive/C3/1994/C39940001615.pdf joint study] conducted by Smithkline Beechams (now trading as GlaxoSmithKline) and the University of Manchester established using real time NMR spectroscopy and other more specialised methods that the drug molecule binds to the bacterial ribosomes in a two stage process, the first of which is the formation of a weak interaction between the ribosome and the amine in the macrocycle.

==Uses==
Zithromycin is a broad-spectrum antibiotic that is able to combat a variety of bacteria that cause a wide variety of bacterial infections namely:

*Chest or lower respiratory tract infections of the lungs and airways such as pneumonia and bronchitis.
* Upper respiratory tract infections of the nasal passages, sinuses and throat such as sinusitis, tonsillitis and pharyngitis.
*Bacterial infections of the middle ear such as otitis media
*Bacterial infections of the skin or soft tissue caused by [http://en.wikipedia.org/wiki/Staphylococcus_aureus| staphylococcus aureus]
*Sexually transmitted infections such as chlamydia

Zithromycin may not be used on people with allegic reactions to macrolide type antibiotics, eg erythromycin, or liver disease. The safety of zithromycin for use during pregnancy has not been established and as such is not recommended. Zithromycin can pass into breast milk and so is also not recommended for use by breast feeding mothers.

Azithromycin can also used to treat early Lyme disease, H. pylori infection, and other infections or to prevent heart infection in patients having dental or other procedures.

==Dose==
Zithromycin should be taken at least one hour before a meal or two hours after a meal to prevent it from binding to food and not being absorbed by the small intestine. Zithromycin should be taken once daily for a short course of five days for the majority of infections. Zithromycin is usually given as a double dose, 500mg, on the first day and as a single dose, 250mg once daily for the remaining four days and can be taken in tablet form or as an intravenous injection.

==Pharmacokinetics==
Zithromycin is acid stable and thus can be taken orally without the need to protect it from the gastric acids. Zithromycin is readily absorbed, and can diffuse into most tissues. Phagocytes in the body take up the zithromycin and actively transport the drug to the site of infection where it is actively released by phagocytosis. Thus large concentrations of zithromycin can be built up at the site of infection, with the concentration being up to 50 times higher in the tissue than in the plasma.

==Side effects==
*Disturbances of the gut such as diarrhoea, constipation, indigestion, nausea, vomiting or abdominal pain
*Headache
*Loss of appetite
*Dizziness
*Thrush infections
*Somnolence (sleepiness)
*Asthenia (weakness or loss of strength)
*Anxiety and agitation
*Hyperactivity
*Paraesthesia (pins and needles)
*Hearing distubances
*Palpitations (awareness of your heartbeat)
*Arrhythmias (abnormal heart beats)
*Arthralgia (pain in the joints)
*Decrease in the number of platelets or white blood cells in the blood
*Allergic skin reactions
*Photosensitivity (abnormal reaction of the skin to light, usually a rash)
*Convulsions (seizures)
*Liver or kidney disorders
*upset stomach
*stomach pain
*mild skin rash
*difficulty breathing or swallowing
*swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
*hoarseness
*yellowing of the skin or eyes
*rapid, pounding, or irregular heartbeat

==Synthesis==
A chemoselective methylation method for preparing zithromycin from 11-aza-10-deoxo-10-dihydroerythromycin and paraformaldehyde is as follows:

[[Image:Synthesis of azithromycin 2.GIF]]

==List of Reference Links==

http://www.sigmaaldrich.com/catalog/search/ProductDetail/FLUKA/75199 <br>
http://www.netdoctor.co.uk/medicines/100003113.html <br>
http://www.chemnetbase.com/scripts/docweb.exe?document+W3y8Rd2kVrC+2+44115#44115
http://en.wikipedia.org/wiki/Azithromycin
http://www.medicinenet.com/azithromycin/article.htm
http://www.rsc.org/ejarchive/C3/1994/C39940001615.pdf
http://www.chlamydiae.com/restricted/docs/labtests/treat_macrolides.asp

SciFinder - Rabinovich, I. M.; Pshenichnikov, V. G.; Kuz'min, I. A. (Otkrytoe Aktsionernoe Obshchestvo Aktsionernoe
Kurganskoe Obshchestvo Meditsinskikh Preparatov i Izdelii "Sintez", Russia). Russ. (2005)
http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a697037.html#if-i-forget

It:Zithromycin

2006-12-08T22:12:22Z

Rx104: /* Side effects */

=Zithromycin=

{|class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" | Structure of Zithromycin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[image:zithromycin.bmp|200px|{{PAGENAME}}]]
|-
! {{chembox header}} align="center" colspan="3" |3D structure
|-
| align="center" colspan="3" bgcolor="#ffffff" |<jmol>
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title1
title2
HEADER NONAME 21-Nov-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 21-Nov-06 0 NONE 4
ATOM 1 C 0 0.648 -1.169 2.459 0.00 0.00 C+0
ATOM 2 C 0 -0.055 -0.745 1.242 0.00 0.00 C+0
ATOM 3 H 0 -1.003 -1.290 1.111 0.00 0.00 H+0
ATOM 4 C 0 -0.442 0.785 1.252 0.00 0.00 C+0
ATOM 5 H 0 -0.937 1.041 0.367 0.00 0.00 H+0
ATOM 6 O 0 0.757 1.554 1.427 0.00 0.00 O+0
ATOM 7 C 0 0.693 2.642 0.491 0.00 0.00 C+0
ATOM 8 H 0 -0.284 3.108 0.584 0.00 0.00 H+0
ATOM 9 C 0 1.791 3.647 0.836 0.00 0.00 C+0
ATOM 10 C 0 1.748 4.824 -0.136 0.00 0.00 C+0
ATOM 11 C 0 0.575 5.747 0.201 0.00 0.00 C+0
ATOM 12 O 0 2.964 5.582 0.024 0.00 0.00 O+0
ATOM 13 C 0 2.845 6.735 -0.812 0.00 0.00 C+0
ATOM 14 C 0 1.669 4.345 -1.580 0.00 0.00 C+0
ATOM 15 H 0 1.298 5.177 -2.202 0.00 0.00 H+0
ATOM 16 O 0 2.992 4.030 -2.042 0.00 0.00 O+0
ATOM 17 C 0 0.768 3.142 -1.793 0.00 0.00 C+0
ATOM 18 H 0 1.074 2.683 -2.763 0.00 0.00 H+0
ATOM 19 C 0 -0.691 3.562 -1.967 0.00 0.00 C+0
ATOM 20 O 0 0.903 2.134 -0.816 0.00 0.00 O+0
ATOM 21 C 0 -1.343 1.017 2.489 0.00 0.00 C+0
ATOM 22 H 0 -1.486 0.194 3.112 0.00 0.00 H+0
ATOM 23 C 0 -0.850 2.242 3.191 0.00 0.00 C+0
ATOM 24 C 0 -2.766 1.358 1.897 0.00 0.00 C+0
ATOM 25 C 0 -3.867 0.329 2.108 0.00 0.00 C+0
ATOM 26 C 0 -4.692 0.264 0.819 0.00 0.00 C+0
ATOM 27 H 0 -4.025 0.156 -0.061 0.00 0.00 H+0
ATOM 28 C 0 -5.445 1.602 0.636 0.00 0.00 C+0
ATOM 29 C 0 -6.154 1.607 -0.719 0.00 0.00 C+0
ATOM 30 C 0 -5.785 -0.826 0.828 0.00 0.00 C+0
ATOM 31 O 0 -6.993 -0.185 1.062 0.00 0.00 O+0
ATOM 32 C 0 -5.523 -1.749 2.106 0.00 0.00 C+0
ATOM 33 C 0 -5.778 -1.600 -0.464 0.00 0.00 C+0
ATOM 34 C 0 -4.669 -2.608 -0.625 0.00 0.00 C+0
ATOM 35 H 0 -3.902 -2.442 0.126 0.00 0.00 H+0
ATOM 36 C 0 -5.265 -4.052 -0.458 0.00 0.00 C+0
ATOM 37 N 0 -4.009 -2.649 -1.976 0.00 0.00 N+0
ATOM 38 C 0 -3.570 -1.215 -2.027 0.00 0.00 C+0
ATOM 39 C 0 -2.775 -3.328 -1.603 0.00 0.00 C+0
ATOM 40 C 0 -1.492 -2.913 -2.336 0.00 0.00 C+0
ATOM 41 H 0 -1.569 -2.024 -3.006 0.00 0.00 H+0
ATOM 42 C 0 -1.098 -4.084 -3.302 0.00 0.00 C+0
ATOM 43 C 0 -0.338 -2.695 -1.357 0.00 0.00 C+0
ATOM 44 C 0 0.063 -1.213 -1.254 0.00 0.00 C+0
ATOM 45 C 0 1.016 -0.946 -2.401 0.00 0.00 C+0
ATOM 46 O 0 -1.057 -0.335 -1.329 0.00 0.00 O+0
ATOM 47 C 0 0.863 -1.024 0.040 0.00 0.00 C+0
ATOM 48 H 0 1.516 -0.109 -0.133 0.00 0.00 H+0
ATOM 49 O 0 1.641 -2.161 0.353 0.00 0.00 O+0
ATOM 50 C 0 2.997 -1.718 0.453 0.00 0.00 C+0
ATOM 51 H 0 3.051 -0.868 1.132 0.00 0.00 H+0
ATOM 52 O 0 3.463 -1.326 -0.837 0.00 0.00 O+0
ATOM 53 C 0 4.746 -0.726 -0.667 0.00 0.00 C+0
ATOM 54 H 0 4.682 0.059 0.087 0.00 0.00 H+0
ATOM 55 C 0 5.203 -0.119 -1.995 0.00 0.00 C+0
ATOM 56 C 0 5.757 -1.783 -0.218 0.00 0.00 C+0
ATOM 57 C 0 5.309 -2.362 1.129 0.00 0.00 C+0
ATOM 58 H 0 5.361 -1.588 1.895 0.00 0.00 H+0
ATOM 59 N 0 6.185 -3.482 1.499 0.00 0.00 N+0
ATOM 60 C 0 6.245 -4.374 0.334 0.00 0.00 C+0
ATOM 61 C 0 7.532 -2.924 1.675 0.00 0.00 C+0
ATOM 62 C 0 3.865 -2.857 0.992 0.00 0.00 C+0
ATOM 63 H 0 3.832 -3.701 0.303 0.00 0.00 H+0
ATOM 64 O 0 3.377 -3.266 2.272 0.00 0.00 O+0
ATOM 65 O 0 -2.943 2.436 1.458 0.00 0.00 O+0
ATOM 66 H 0 -0.009 -1.046 3.320 0.00 0.00 H+0
ATOM 67 H 0 0.934 -2.217 2.367 0.00 0.00 H+0
ATOM 68 H 0 1.542 -0.559 2.593 0.00 0.00 H+0
ATOM 69 H 0 1.642 4.009 1.856 0.00 0.00 H+0
ATOM 70 H 0 2.765 3.156 0.776 0.00 0.00 H+0
ATOM 71 H 0 0.772 6.255 1.145 0.00 0.00 H+0
ATOM 72 H 0 0.454 6.485 -0.592 0.00 0.00 H+0
ATOM 73 H 0 -0.337 5.157 0.290 0.00 0.00 H+0
ATOM 74 H 0 3.784 7.288 -0.805 0.00 0.00 H+0
ATOM 75 H 0 2.615 6.423 -1.831 0.00 0.00 H+0
ATOM 76 H 0 2.045 7.373 -0.438 0.00 0.00 H+0
ATOM 77 H 0 2.905 3.731 -2.957 0.00 0.00 H+0
ATOM 78 H 0 -0.779 4.218 -2.834 0.00 0.00 H+0
ATOM 79 H 0 -1.308 2.676 -2.118 0.00 0.00 H+0
ATOM 80 H 0 -1.026 4.091 -1.075 0.00 0.00 H+0
ATOM 81 H 0 -0.936 3.101 2.526 0.00 0.00 H+0
ATOM 82 H 0 -1.449 2.414 4.086 0.00 0.00 H+0
ATOM 83 H 0 0.193 2.103 3.474 0.00 0.00 H+0
ATOM 84 H 0 -3.414 -0.608 2.297 0.00 0.00 H+0
ATOM 85 H 0 -4.512 0.647 2.995 0.00 0.00 H+0
ATOM 86 H 0 -6.181 1.717 1.432 0.00 0.00 H+0
ATOM 87 H 0 -4.734 2.428 0.677 0.00 0.00 H+0
ATOM 88 H 0 -6.594 2.589 -0.896 0.00 0.00 H+0
ATOM 89 H 0 -5.434 1.384 -1.507 0.00 0.00 H+0
ATOM 90 H 0 -6.940 0.852 -0.721 0.00 0.00 H+0
ATOM 91 H 0 -7.676 -0.870 1.067 0.00 0.00 H+0
ATOM 92 H 0 -5.580 -1.142 3.009 0.00 0.00 H+0
ATOM 93 H 0 -6.278 -2.534 2.147 0.00 0.00 H+0
ATOM 94 H 0 -4.533 -2.199 2.032 0.00 0.00 H+0
ATOM 95 H 0 -6.742 -2.171 -0.484 0.00 0.00 H+0
ATOM 96 H 0 -5.836 -0.955 -1.266 0.00 0.00 H+0
ATOM 97 H 0 -6.029 -4.220 -1.217 0.00 0.00 H+0
ATOM 98 H 0 -4.470 -4.789 -0.572 0.00 0.00 H+0
ATOM 99 H 0 -5.710 -4.149 0.533 0.00 0.00 H+0
ATOM 100 H 0 -3.026 -0.969 -1.115 0.00 0.00 H+0
ATOM 101 H 0 -2.920 -1.065 -2.889 0.00 0.00 H+0
ATOM 102 H 0 -4.444 -0.570 -2.115 0.00 0.00 H+0
ATOM 103 H 0 -2.546 -3.132 -0.486 0.00 0.00 H+0
ATOM 104 H 0 -2.915 -4.430 -1.755 0.00 0.00 H+0
ATOM 105 H 0 -1.905 -4.254 -4.015 0.00 0.00 H+0
ATOM 106 H 0 -0.188 -3.820 -3.840 0.00 0.00 H+0
ATOM 107 H 0 -0.928 -4.991 -2.723 0.00 0.00 H+0
ATOM 108 H 0 -0.699 -3.031 -0.383 0.00 0.00 H+0
ATOM 109 H 0 0.465 -3.306 -1.713 0.00 0.00 H+0
ATOM 110 H 0 0.480 -1.032 -3.347 0.00 0.00 H+0
ATOM 111 H 0 1.426 0.059 -2.306 0.00 0.00 H+0
ATOM 112 H 0 1.828 -1.673 -2.376 0.00 0.00 H+0
ATOM 113 H 0 -1.480 -0.493 -2.184 0.00 0.00 H+0
ATOM 114 H 0 4.486 0.638 -2.314 0.00 0.00 H+0
ATOM 115 H 0 6.183 0.340 -1.867 0.00 0.00 H+0
ATOM 116 H 0 5.264 -0.902 -2.751 0.00 0.00 H+0
ATOM 117 H 0 5.806 -2.580 -0.960 0.00 0.00 H+0
ATOM 118 H 0 6.740 -1.324 -0.109 0.00 0.00 H+0
ATOM 119 H 0 6.776 -5.287 0.603 0.00 0.00 H+0
ATOM 120 H 0 5.234 -4.623 0.014 0.00 0.00 H+0
ATOM 121 H 0 6.771 -3.874 -0.479 0.00 0.00 H+0
ATOM 122 H 0 7.491 -2.087 2.371 0.00 0.00 H+0
ATOM 123 H 0 8.196 -3.694 2.070 0.00 0.00 H+0
ATOM 124 H 0 7.910 -2.578 0.713 0.00 0.00 H+0
ATOM 125 H 0 2.468 -3.569 2.140 0.00 0.00 H+0
CONECT 1 2 66 67 68 NONE 130
CONECT 2 1 3 47 4 NONE 131
CONECT 4 2 5 6 21 NONE 132
CONECT 6 4 7 0 0 NONE 133
CONECT 7 6 8 20 9 NONE 134
CONECT 9 7 10 69 70 NONE 135
CONECT 10 9 11 12 14 NONE 136
CONECT 11 10 71 72 73 NONE 137
CONECT 12 10 13 0 0 NONE 138
CONECT 13 12 74 75 76 NONE 139
CONECT 14 10 15 16 17 NONE 140
CONECT 16 14 77 0 0 NONE 141
CONECT 17 14 18 19 20 NONE 142
CONECT 19 17 78 79 80 NONE 143
CONECT 20 17 7 0 0 NONE 144
CONECT 21 4 22 23 24 NONE 145
CONECT 23 21 81 82 83 NONE 146
CONECT 24 21 25 65 0 NONE 147
CONECT 25 24 26 84 85 NONE 148
CONECT 26 25 27 28 30 NONE 149
CONECT 28 26 29 86 87 NONE 150
CONECT 29 28 88 89 90 NONE 151
CONECT 30 26 31 32 33 NONE 152
CONECT 31 30 91 0 0 NONE 153
CONECT 32 30 92 93 94 NONE 154
CONECT 33 30 34 95 96 NONE 155
CONECT 34 33 35 36 37 NONE 156
CONECT 36 34 97 98 99 NONE 157
CONECT 37 34 38 39 0 NONE 158
CONECT 38 37 100 101 102 NONE 159
CONECT 39 37 40 103 104 NONE 160
CONECT 40 39 41 42 43 NONE 161
CONECT 42 40 105 106 107 NONE 162
CONECT 43 40 44 108 109 NONE 163
CONECT 44 43 45 46 47 NONE 164
CONECT 45 44 110 111 112 NONE 165
CONECT 46 44 113 0 0 NONE 166
CONECT 47 44 48 2 49 NONE 167
CONECT 49 47 50 0 0 NONE 168
CONECT 50 49 51 62 52 NONE 169
CONECT 52 50 53 0 0 NONE 170
CONECT 53 52 54 55 56 NONE 171
CONECT 55 53 114 115 116 NONE 172
CONECT 56 53 57 117 118 NONE 173
CONECT 57 56 58 59 62 NONE 174
CONECT 59 57 60 61 0 NONE 175
CONECT 60 59 119 120 121 NONE 176
CONECT 61 59 122 123 124 NONE 177
CONECT 62 57 63 50 64 NONE 178
CONECT 64 62 125 0 0 NONE 179
CONECT 65 24 0 0 0 NONE 180
END NONE 181

M END</inlineContents>
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|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|9-deoxy-9a-aza-9a-methyl-9a-<br> homoerythromycin A
|-
| colspan="1" |Other names
| colspan="2"|Azithromycin
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2"|83905-01-5
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2"|C<sub>38</sub>H<sub>72</sub>N<sub>2</sub>O<sub>12</sub>
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2"|C[C@H]1[C@H](O[C@H]3C[C@@]<br>(C)(OC)[C@@H](O)[C@H](C)O3)<br>[C@@H](C)C(C[C@H](CC)[C@](O)<br>(C)C[C@@H](C)N(C)C[C@H](C)<br>C[C@@](C)(O)[C@@H]1O[C@@H]2O<br>[C@H](C)C[C@H](N(C)C)[C@H]2O)=O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2"|748.98g/mol
|-
| colspan="1" |Appearance
| colspan="2"|Crystalline structure
|-
| colspan="1" |Melting point
| colspan="2"|136°C to 155°C
|-
|}

Confusingly, this popular anti-biotic is also known as azithromycin, and is marketed as zithromax by Pfizer. According to their website, it's the most widely sold antibiotic in the world. It is a member of a large class of antibiotics derived from erythromycin, which differs only from azithromycin in that the nitrogen in the macrocycle is replaced by a carbonyl group. They have similar activities with respect to bacteria and appear to work in much the same way, but azithromycin is much more readily accepted by the body, causing fewer and less severe side effects. This means that even though the drug itself is more expensive, the overall cost of its' use is lower as less follow up appointments are required.

==Mode of action==
Zithromycin is a macrolide antibiotic which works by interfering with bacterial protein synthesis by binding to the 50S subunit of the bacterial ribosome, thus inhibiting the translation of mRNA. This inhibits the growth of the bacteria, their ability to replicate and increase in numbers. This therefore stops the spread of infection and allows the body's immune system to kill any remaining bacteria.

In 1994 a [http://www.rsc.org/ejarchive/C3/1994/C39940001615.pdf joint study] conducted by Smithkline Beechams (now trading as GlaxoSmithKline) and the University of Manchester established using real time NMR spectroscopy and other more specialised methods that the drug molecule binds to the bacterial ribosomes in a two stage process, the first of which is the formation of a weak interaction between the ribosome and the amine in the macrocycle.

==Uses==
Zithromycin is a broad-spectrum antibiotic that is able to combat a variety of bacteria that cause a wide variety of bacterial infections namely:

*Chest or lower respiratory tract infections of the lungs and airways such as pneumonia and bronchitis.
* Upper respiratory tract infections of the nasal passages, sinuses and throat such as sinusitis, tonsillitis and pharyngitis.
*Bacterial infections of the middle ear such as otitis media
*Bacterial infections of the skin or soft tissue caused by [http://en.wikipedia.org/wiki/Staphylococcus_aureus| staphylococcus aureus]
*Sexually transmitted infections such as chlamydia

Zithromycin may not be used on people with allegic reactions to macrolide type antibiotics, eg erythromycin, or liver disease. The safety of zithromycin for use during pregnancy has not been established and as such is not recommended. Zithromycin can pass into breast milk and so is also not recommended for use by breast feeding mothers.

Azithromycin can also used to treat early Lyme disease, H. pylori infection, and other infections or to prevent heart infection in patients having dental or other procedures.

==Dose==
Zithromycin should be taken at least one hour before a meal or two hours after a meal to prevent it from binding to food and not being absorbed by the small intestine. Zithromycin should be taken once daily for a short course of five days for the majority of infections. Zithromycin is usually given as a double dose, 500mg, on the first day and as a single dose, 250mg once daily for the remaining four days and can be taken in tablet form or as an intravenous injection.

==Pharmacokinetics==
Zithromycin is acid stable and thus can be taken orally without the need to protect it from the gastric acids. Zithromycin is readily absorbed, and can diffuse into most tissues. Phagocytes in the body take up the zithromycin and actively transport the drug to the site of infection where it is actively released by phagocytosis. Thus large concentrations of zithromycin can be built up at the site of infection, with the concentration being up to 50 times higher in the tissue than in the plasma.

==Side effects==
*Disturbances of the gut such as diarrhoea, constipation, indigestion, nausea, vomiting or abdominal pain
*Headache
*Loss of appetite
*Dizziness
*Thrush infections
*Somnolence (sleepiness)
*Asthenia (weakness or loss of strength)
*Anxiety and agitation
*Hyperactivity
*Paraesthesia (pins and needles)
*Hearing distubances
*Palpitations (awareness of your heartbeat)
*Arrhythmias (abnormal heart beats)
*Arthralgia (pain in the joints)
*Decrease in the number of platelets or white blood cells in the blood
*Allergic skin reactions
*Photosensitivity (abnormal reaction of the skin to light, usually a rash)
*Convulsions (seizures)
*Liver or kidney disorders
*upset stomach
*stomach pain
*mild skin rash
*difficulty breathing or swallowing
*swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
*hoarseness
*yellowing of the skin or eyes
*rapid, pounding, or irregular heartbeat

==Synthesis==
A chemoselective methylation method for preparing zithromycin from 11-aza-10-deoxo-10-dihydroerythromycin and paraformaldehyde is as follows:

[[Image:Synthesis of azithromycin 2.GIF]]

==List of Reference Links==

http://www.sigmaaldrich.com/catalog/search/ProductDetail/FLUKA/75199 <br>
http://www.netdoctor.co.uk/medicines/100003113.html <br>
http://www.chemnetbase.com/scripts/docweb.exe?document+W3y8Rd2kVrC+2+44115#44115
http://en.wikipedia.org/wiki/Azithromycin
http://www.medicinenet.com/azithromycin/article.htm
http://www.rsc.org/ejarchive/C3/1994/C39940001615.pdf
http://www.chlamydiae.com/restricted/docs/labtests/treat_macrolides.asp

SciFinder - Rabinovich, I. M.; Pshenichnikov, V. G.; Kuz'min, I. A. (Otkrytoe Aktsionernoe Obshchestvo Aktsionernoe
Kurganskoe Obshchestvo Meditsinskikh Preparatov i Izdelii "Sintez", Russia). Russ. (2005)

It:Zithromycin

2006-12-08T22:09:05Z

Rx104: /* Uses */

=Zithromycin=

{|class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" | Structure of Zithromycin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[image:zithromycin.bmp|200px|{{PAGENAME}}]]
|-
! {{chembox header}} align="center" colspan="3" |3D structure
|-
| align="center" colspan="3" bgcolor="#ffffff" |<jmol>
<jmolApplet>
<size>300</size>
<color>white</color>
<script>zoom 80; bns on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
title1
title2
HEADER NONAME 21-Nov-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 21-Nov-06 0 NONE 4
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ATOM 3 H 0 -1.003 -1.290 1.111 0.00 0.00 H+0
ATOM 4 C 0 -0.442 0.785 1.252 0.00 0.00 C+0
ATOM 5 H 0 -0.937 1.041 0.367 0.00 0.00 H+0
ATOM 6 O 0 0.757 1.554 1.427 0.00 0.00 O+0
ATOM 7 C 0 0.693 2.642 0.491 0.00 0.00 C+0
ATOM 8 H 0 -0.284 3.108 0.584 0.00 0.00 H+0
ATOM 9 C 0 1.791 3.647 0.836 0.00 0.00 C+0
ATOM 10 C 0 1.748 4.824 -0.136 0.00 0.00 C+0
ATOM 11 C 0 0.575 5.747 0.201 0.00 0.00 C+0
ATOM 12 O 0 2.964 5.582 0.024 0.00 0.00 O+0
ATOM 13 C 0 2.845 6.735 -0.812 0.00 0.00 C+0
ATOM 14 C 0 1.669 4.345 -1.580 0.00 0.00 C+0
ATOM 15 H 0 1.298 5.177 -2.202 0.00 0.00 H+0
ATOM 16 O 0 2.992 4.030 -2.042 0.00 0.00 O+0
ATOM 17 C 0 0.768 3.142 -1.793 0.00 0.00 C+0
ATOM 18 H 0 1.074 2.683 -2.763 0.00 0.00 H+0
ATOM 19 C 0 -0.691 3.562 -1.967 0.00 0.00 C+0
ATOM 20 O 0 0.903 2.134 -0.816 0.00 0.00 O+0
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ATOM 25 C 0 -3.867 0.329 2.108 0.00 0.00 C+0
ATOM 26 C 0 -4.692 0.264 0.819 0.00 0.00 C+0
ATOM 27 H 0 -4.025 0.156 -0.061 0.00 0.00 H+0
ATOM 28 C 0 -5.445 1.602 0.636 0.00 0.00 C+0
ATOM 29 C 0 -6.154 1.607 -0.719 0.00 0.00 C+0
ATOM 30 C 0 -5.785 -0.826 0.828 0.00 0.00 C+0
ATOM 31 O 0 -6.993 -0.185 1.062 0.00 0.00 O+0
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ATOM 44 C 0 0.063 -1.213 -1.254 0.00 0.00 C+0
ATOM 45 C 0 1.016 -0.946 -2.401 0.00 0.00 C+0
ATOM 46 O 0 -1.057 -0.335 -1.329 0.00 0.00 O+0
ATOM 47 C 0 0.863 -1.024 0.040 0.00 0.00 C+0
ATOM 48 H 0 1.516 -0.109 -0.133 0.00 0.00 H+0
ATOM 49 O 0 1.641 -2.161 0.353 0.00 0.00 O+0
ATOM 50 C 0 2.997 -1.718 0.453 0.00 0.00 C+0
ATOM 51 H 0 3.051 -0.868 1.132 0.00 0.00 H+0
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ATOM 53 C 0 4.746 -0.726 -0.667 0.00 0.00 C+0
ATOM 54 H 0 4.682 0.059 0.087 0.00 0.00 H+0
ATOM 55 C 0 5.203 -0.119 -1.995 0.00 0.00 C+0
ATOM 56 C 0 5.757 -1.783 -0.218 0.00 0.00 C+0
ATOM 57 C 0 5.309 -2.362 1.129 0.00 0.00 C+0
ATOM 58 H 0 5.361 -1.588 1.895 0.00 0.00 H+0
ATOM 59 N 0 6.185 -3.482 1.499 0.00 0.00 N+0
ATOM 60 C 0 6.245 -4.374 0.334 0.00 0.00 C+0
ATOM 61 C 0 7.532 -2.924 1.675 0.00 0.00 C+0
ATOM 62 C 0 3.865 -2.857 0.992 0.00 0.00 C+0
ATOM 63 H 0 3.832 -3.701 0.303 0.00 0.00 H+0
ATOM 64 O 0 3.377 -3.266 2.272 0.00 0.00 O+0
ATOM 65 O 0 -2.943 2.436 1.458 0.00 0.00 O+0
ATOM 66 H 0 -0.009 -1.046 3.320 0.00 0.00 H+0
ATOM 67 H 0 0.934 -2.217 2.367 0.00 0.00 H+0
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ATOM 69 H 0 1.642 4.009 1.856 0.00 0.00 H+0
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ATOM 71 H 0 0.772 6.255 1.145 0.00 0.00 H+0
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ATOM 73 H 0 -0.337 5.157 0.290 0.00 0.00 H+0
ATOM 74 H 0 3.784 7.288 -0.805 0.00 0.00 H+0
ATOM 75 H 0 2.615 6.423 -1.831 0.00 0.00 H+0
ATOM 76 H 0 2.045 7.373 -0.438 0.00 0.00 H+0
ATOM 77 H 0 2.905 3.731 -2.957 0.00 0.00 H+0
ATOM 78 H 0 -0.779 4.218 -2.834 0.00 0.00 H+0
ATOM 79 H 0 -1.308 2.676 -2.118 0.00 0.00 H+0
ATOM 80 H 0 -1.026 4.091 -1.075 0.00 0.00 H+0
ATOM 81 H 0 -0.936 3.101 2.526 0.00 0.00 H+0
ATOM 82 H 0 -1.449 2.414 4.086 0.00 0.00 H+0
ATOM 83 H 0 0.193 2.103 3.474 0.00 0.00 H+0
ATOM 84 H 0 -3.414 -0.608 2.297 0.00 0.00 H+0
ATOM 85 H 0 -4.512 0.647 2.995 0.00 0.00 H+0
ATOM 86 H 0 -6.181 1.717 1.432 0.00 0.00 H+0
ATOM 87 H 0 -4.734 2.428 0.677 0.00 0.00 H+0
ATOM 88 H 0 -6.594 2.589 -0.896 0.00 0.00 H+0
ATOM 89 H 0 -5.434 1.384 -1.507 0.00 0.00 H+0
ATOM 90 H 0 -6.940 0.852 -0.721 0.00 0.00 H+0
ATOM 91 H 0 -7.676 -0.870 1.067 0.00 0.00 H+0
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ATOM 93 H 0 -6.278 -2.534 2.147 0.00 0.00 H+0
ATOM 94 H 0 -4.533 -2.199 2.032 0.00 0.00 H+0
ATOM 95 H 0 -6.742 -2.171 -0.484 0.00 0.00 H+0
ATOM 96 H 0 -5.836 -0.955 -1.266 0.00 0.00 H+0
ATOM 97 H 0 -6.029 -4.220 -1.217 0.00 0.00 H+0
ATOM 98 H 0 -4.470 -4.789 -0.572 0.00 0.00 H+0
ATOM 99 H 0 -5.710 -4.149 0.533 0.00 0.00 H+0
ATOM 100 H 0 -3.026 -0.969 -1.115 0.00 0.00 H+0
ATOM 101 H 0 -2.920 -1.065 -2.889 0.00 0.00 H+0
ATOM 102 H 0 -4.444 -0.570 -2.115 0.00 0.00 H+0
ATOM 103 H 0 -2.546 -3.132 -0.486 0.00 0.00 H+0
ATOM 104 H 0 -2.915 -4.430 -1.755 0.00 0.00 H+0
ATOM 105 H 0 -1.905 -4.254 -4.015 0.00 0.00 H+0
ATOM 106 H 0 -0.188 -3.820 -3.840 0.00 0.00 H+0
ATOM 107 H 0 -0.928 -4.991 -2.723 0.00 0.00 H+0
ATOM 108 H 0 -0.699 -3.031 -0.383 0.00 0.00 H+0
ATOM 109 H 0 0.465 -3.306 -1.713 0.00 0.00 H+0
ATOM 110 H 0 0.480 -1.032 -3.347 0.00 0.00 H+0
ATOM 111 H 0 1.426 0.059 -2.306 0.00 0.00 H+0
ATOM 112 H 0 1.828 -1.673 -2.376 0.00 0.00 H+0
ATOM 113 H 0 -1.480 -0.493 -2.184 0.00 0.00 H+0
ATOM 114 H 0 4.486 0.638 -2.314 0.00 0.00 H+0
ATOM 115 H 0 6.183 0.340 -1.867 0.00 0.00 H+0
ATOM 116 H 0 5.264 -0.902 -2.751 0.00 0.00 H+0
ATOM 117 H 0 5.806 -2.580 -0.960 0.00 0.00 H+0
ATOM 118 H 0 6.740 -1.324 -0.109 0.00 0.00 H+0
ATOM 119 H 0 6.776 -5.287 0.603 0.00 0.00 H+0
ATOM 120 H 0 5.234 -4.623 0.014 0.00 0.00 H+0
ATOM 121 H 0 6.771 -3.874 -0.479 0.00 0.00 H+0
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ATOM 123 H 0 8.196 -3.694 2.070 0.00 0.00 H+0
ATOM 124 H 0 7.910 -2.578 0.713 0.00 0.00 H+0
ATOM 125 H 0 2.468 -3.569 2.140 0.00 0.00 H+0
CONECT 1 2 66 67 68 NONE 130
CONECT 2 1 3 47 4 NONE 131
CONECT 4 2 5 6 21 NONE 132
CONECT 6 4 7 0 0 NONE 133
CONECT 7 6 8 20 9 NONE 134
CONECT 9 7 10 69 70 NONE 135
CONECT 10 9 11 12 14 NONE 136
CONECT 11 10 71 72 73 NONE 137
CONECT 12 10 13 0 0 NONE 138
CONECT 13 12 74 75 76 NONE 139
CONECT 14 10 15 16 17 NONE 140
CONECT 16 14 77 0 0 NONE 141
CONECT 17 14 18 19 20 NONE 142
CONECT 19 17 78 79 80 NONE 143
CONECT 20 17 7 0 0 NONE 144
CONECT 21 4 22 23 24 NONE 145
CONECT 23 21 81 82 83 NONE 146
CONECT 24 21 25 65 0 NONE 147
CONECT 25 24 26 84 85 NONE 148
CONECT 26 25 27 28 30 NONE 149
CONECT 28 26 29 86 87 NONE 150
CONECT 29 28 88 89 90 NONE 151
CONECT 30 26 31 32 33 NONE 152
CONECT 31 30 91 0 0 NONE 153
CONECT 32 30 92 93 94 NONE 154
CONECT 33 30 34 95 96 NONE 155
CONECT 34 33 35 36 37 NONE 156
CONECT 36 34 97 98 99 NONE 157
CONECT 37 34 38 39 0 NONE 158
CONECT 38 37 100 101 102 NONE 159
CONECT 39 37 40 103 104 NONE 160
CONECT 40 39 41 42 43 NONE 161
CONECT 42 40 105 106 107 NONE 162
CONECT 43 40 44 108 109 NONE 163
CONECT 44 43 45 46 47 NONE 164
CONECT 45 44 110 111 112 NONE 165
CONECT 46 44 113 0 0 NONE 166
CONECT 47 44 48 2 49 NONE 167
CONECT 49 47 50 0 0 NONE 168
CONECT 50 49 51 62 52 NONE 169
CONECT 52 50 53 0 0 NONE 170
CONECT 53 52 54 55 56 NONE 171
CONECT 55 53 114 115 116 NONE 172
CONECT 56 53 57 117 118 NONE 173
CONECT 57 56 58 59 62 NONE 174
CONECT 59 57 60 61 0 NONE 175
CONECT 60 59 119 120 121 NONE 176
CONECT 61 59 122 123 124 NONE 177
CONECT 62 57 63 50 64 NONE 178
CONECT 64 62 125 0 0 NONE 179
CONECT 65 24 0 0 0 NONE 180
END NONE 181

M END</inlineContents>
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|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|9-deoxy-9a-aza-9a-methyl-9a-<br> homoerythromycin A
|-
| colspan="1" |Other names
| colspan="2"|Azithromycin
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2"|83905-01-5
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2"|C<sub>38</sub>H<sub>72</sub>N<sub>2</sub>O<sub>12</sub>
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2"|C[C@H]1[C@H](O[C@H]3C[C@@]<br>(C)(OC)[C@@H](O)[C@H](C)O3)<br>[C@@H](C)C(C[C@H](CC)[C@](O)<br>(C)C[C@@H](C)N(C)C[C@H](C)<br>C[C@@](C)(O)[C@@H]1O[C@@H]2O<br>[C@H](C)C[C@H](N(C)C)[C@H]2O)=O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2"|748.98g/mol
|-
| colspan="1" |Appearance
| colspan="2"|Crystalline structure
|-
| colspan="1" |Melting point
| colspan="2"|136°C to 155°C
|-
|}

Confusingly, this popular anti-biotic is also known as azithromycin, and is marketed as zithromax by Pfizer. According to their website, it's the most widely sold antibiotic in the world. It is a member of a large class of antibiotics derived from erythromycin, which differs only from azithromycin in that the nitrogen in the macrocycle is replaced by a carbonyl group. They have similar activities with respect to bacteria and appear to work in much the same way, but azithromycin is much more readily accepted by the body, causing fewer and less severe side effects. This means that even though the drug itself is more expensive, the overall cost of its' use is lower as less follow up appointments are required.

==Mode of action==
Zithromycin is a macrolide antibiotic which works by interfering with bacterial protein synthesis by binding to the 50S subunit of the bacterial ribosome, thus inhibiting the translation of mRNA. This inhibits the growth of the bacteria, their ability to replicate and increase in numbers. This therefore stops the spread of infection and allows the body's immune system to kill any remaining bacteria.

In 1994 a [http://www.rsc.org/ejarchive/C3/1994/C39940001615.pdf joint study] conducted by Smithkline Beechams (now trading as GlaxoSmithKline) and the University of Manchester established using real time NMR spectroscopy and other more specialised methods that the drug molecule binds to the bacterial ribosomes in a two stage process, the first of which is the formation of a weak interaction between the ribosome and the amine in the macrocycle.

==Uses==
Zithromycin is a broad-spectrum antibiotic that is able to combat a variety of bacteria that cause a wide variety of bacterial infections namely:

*Chest or lower respiratory tract infections of the lungs and airways such as pneumonia and bronchitis.
* Upper respiratory tract infections of the nasal passages, sinuses and throat such as sinusitis, tonsillitis and pharyngitis.
*Bacterial infections of the middle ear such as otitis media
*Bacterial infections of the skin or soft tissue caused by [http://en.wikipedia.org/wiki/Staphylococcus_aureus| staphylococcus aureus]
*Sexually transmitted infections such as chlamydia

Zithromycin may not be used on people with allegic reactions to macrolide type antibiotics, eg erythromycin, or liver disease. The safety of zithromycin for use during pregnancy has not been established and as such is not recommended. Zithromycin can pass into breast milk and so is also not recommended for use by breast feeding mothers.

Azithromycin can also used to treat early Lyme disease, H. pylori infection, and other infections or to prevent heart infection in patients having dental or other procedures.

==Dose==
Zithromycin should be taken at least one hour before a meal or two hours after a meal to prevent it from binding to food and not being absorbed by the small intestine. Zithromycin should be taken once daily for a short course of five days for the majority of infections. Zithromycin is usually given as a double dose, 500mg, on the first day and as a single dose, 250mg once daily for the remaining four days and can be taken in tablet form or as an intravenous injection.

==Pharmacokinetics==
Zithromycin is acid stable and thus can be taken orally without the need to protect it from the gastric acids. Zithromycin is readily absorbed, and can diffuse into most tissues. Phagocytes in the body take up the zithromycin and actively transport the drug to the site of infection where it is actively released by phagocytosis. Thus large concentrations of zithromycin can be built up at the site of infection, with the concentration being up to 50 times higher in the tissue than in the plasma.

==Side effects==
*Disturbances of the gut such as diarrhoea, constipation, indigestion, nausea, vomiting or abdominal pain
*Headache
*Loss of appetite
*Dizziness
*Thrush infections
*Somnolence (sleepiness)
*Asthenia (weakness or loss of strength)
*Anxiety and agitation
*Hyperactivity
*Paraesthesia (pins and needles)
*Hearing distubances
*Palpitations (awareness of your heartbeat)
*Arrhythmias (abnormal heart beats)
*Arthralgia (pain in the joints)
*Decrease in the number of platelets or white blood cells in the blood
*Allergic skin reactions
*Photosensitivity (abnormal reaction of the skin to light, usually a rash)
*Convulsions (seizures)
*Liver or kidney disorders

==Synthesis==
A chemoselective methylation method for preparing zithromycin from 11-aza-10-deoxo-10-dihydroerythromycin and paraformaldehyde is as follows:

[[Image:Synthesis of azithromycin 2.GIF]]

==List of Reference Links==

http://www.sigmaaldrich.com/catalog/search/ProductDetail/FLUKA/75199 <br>
http://www.netdoctor.co.uk/medicines/100003113.html <br>
http://www.chemnetbase.com/scripts/docweb.exe?document+W3y8Rd2kVrC+2+44115#44115
http://en.wikipedia.org/wiki/Azithromycin
http://www.medicinenet.com/azithromycin/article.htm
http://www.rsc.org/ejarchive/C3/1994/C39940001615.pdf
http://www.chlamydiae.com/restricted/docs/labtests/treat_macrolides.asp

SciFinder - Rabinovich, I. M.; Pshenichnikov, V. G.; Kuz'min, I. A. (Otkrytoe Aktsionernoe Obshchestvo Aktsionernoe
Kurganskoe Obshchestvo Meditsinskikh Preparatov i Izdelii "Sintez", Russia). Russ. (2005)

It:Lipitor

2006-12-08T22:01:05Z

Rx104: /* Reference Link */

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Systematic IUPAC Name
|-
| Systematic Iupac Name
| colspan="2"| [R-(R*, R*)]-2-(4-fluorophenyl)-beta,<br> delta-dihydroxy-5- <br>(1-methylethyl)-3-phenyl-4- <br>[(phenylamino)carbonyl]-1H-<br> pyrrole-1-heptanoic acid|-
|-
! {{chembox header}} colspan="3"| Identifiers
|-
| CAS registry number|CAS number
| colspan="2" | 134523-00-5
|-
| CAS registry number|ATC Code
| colspan="2" | C10AA05
|-
| CAS registry number|Pub Chem
| colspan="2" | 60823
|-
| CAS registry number|Drug Bank
| colspan="2" | APRD00055
|-
|-
! {{chembox header}} colspan="3"| Chemical Data
|-
| Chemical formula|Molecular formula
| colspan="2" | C<sub>33</sub>H<sub>34</sub>N<sub>2</sub>O<sub>5</sub>F
|-
| Molar mass
| colspan="2" | 558.64 g/mol
|-
! {{chembox header}} colspan="3"| Pharmacokinetic data
|-
| CAS registry number|Bioavailability
| colspan="2" | 15 %
|-
| CAS registry number|Metabolism
| colspan="2" | Liver
|-
| CAS registry number|Half Life
| colspan="2" | 14 Hours
|-
| CAS registry number|Excretion
| colspan="2" | Bile
|-
! {{chembox header}} colspan="3"| Therapeutic considerations
|-
| CAS registry number|Pregnancy Cat.
| colspan="2" | D(AU) X(US)
|-
| CAS registry number|Legal Status
| colspan="2" | S4(AU) POM(UK) ℞-only(US)
|-
| CAS registry number|Route
| colspan="2" | Oral

|}

Lipitor (Atorvastatin also a type of chiral drug) is a cholesterol-lowering medication (a type of HMG CoA reductase inhibitor) which belongs to a lass of medicine called statins. Lipitor is the most potent of all statins.It was introduced in 1996. It is used to block the production of cholesterol in the human body. Lipitor is also used to increase levels of HDL (good) cholesterol in the blood. This is important as it reduces the risk of hardening arteries which can lead to heart attacks, strokes and peripheral vascular disease.
[http://www.lipitor.com/cwp/appmanager/lipitor/lipitorDesktop 1]

Since 1996, Lipitor (lipitor marked jointly by Parke Davis and Pfizer, co-promoted by Warner-Lambert) had enormous growth in the international market of chiral drug. It has achieved sales up to $4 billion in 1999 (around 3 years of its market) which marked one of the best selling drug in US alone(41% of the US market). Lipitor has reached the worldwide market of cholesterol-reducing drug as the most potent drug in its class.

== How does it works ==

LDL (low density lipoprotein) cholesterol is not water soluble thus it travels in the human body in the form of lipoprotein. Once it reaches the human artery, it can cause a buildup of plaque in the lumen wall, constricting the blood flow, thus induces atherosclerosis (thickening of the arteries). Lipitor will competitively inhibit an enzyme in the liver (hepatic tissue) which is used to produce the LDL cholesterol.

== Synthesis ==
[[Image:atorvastatin synthesis.JPG]][http://organicdivision.org/essays_2001/schaus.pdf Synthesis]
<br>
An aldehyde is reacted with an enol ether to form alcohol '''15'''. The transesterification of the alcohol with NaOMe and methanol results in the methyl ester '''16'''. The enolate of tert-butylacetate ('''17''') is added to the methyl ester furthered by directed reduction to form the syn-1,3-diol '''18'''. The resultant is treated with NaOH in refluxing Toluene to form the cycled hydroxylactone '''19'''. Lastly, acid is used to 'open' the hydroxylactone thus forming a sodium salt which is treated with CaCl2.H2O to yield the atorvastatin (LIPITOR)
== Structure ==

[[Image:lipitor3.gif|centre|100|image produced in chemdraw]]

== 3D Structure ==

<jmol>
<jmolApplet>
<size>500</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
title1
title2
ATOM 1 O 0 -4.424 1.493 1.749 0.00 0.00 O+0
ATOM 2 C 0 -4.300 0.218 1.115 0.00 0.00 C+0
ATOM 3 H 0 -4.644 -0.561 1.796 0.00 0.00 H+0
ATOM 4 C 0 -5.150 0.196 -0.157 0.00 0.00 C+0
ATOM 5 C 0 -6.629 0.321 0.216 0.00 0.00 C+0
ATOM 6 H 0 -6.891 -0.462 0.928 0.00 0.00 H+0
ATOM 7 O 0 -6.865 1.601 0.806 0.00 0.00 O+0
ATOM 8 C 0 -7.486 0.174 -1.043 0.00 0.00 C+0
ATOM 9 C 0 -8.944 0.174 -0.661 0.00 0.00 C+0
ATOM 10 O 0 -9.267 0.281 0.510 0.00 0.00 O-1
ATOM 11 O 0 -9.800 0.066 -1.522 0.00 0.00 O+0
ATOM 12 C 0 -2.834 -0.031 0.753 0.00 0.00 C+0
ATOM 13 C 0 -2.003 -0.133 2.034 0.00 0.00 C+0
ATOM 14 N 0 -0.600 -0.372 1.688 0.00 0.00 N+0
ATOM 15 C 0 0.314 0.596 1.478 0.00 0.00 C+0
ATOM 16 C 0 1.511 0.010 1.177 0.00 0.00 C+0
ATOM 17 C 0 2.779 0.692 0.877 0.00 0.00 C+0
ATOM 18 N 0 2.820 2.037 0.803 0.00 0.00 N+0
ATOM 19 C 0 4.044 2.691 0.633 0.00 0.00 C+0
ATOM 20 C 0 4.117 3.842 -0.142 0.00 0.00 C+0
ATOM 21 C 0 5.328 4.485 -0.307 0.00 0.00 C+0
ATOM 22 C 0 6.467 3.986 0.297 0.00 0.00 C+0
ATOM 23 C 0 6.398 2.841 1.069 0.00 0.00 C+0
ATOM 24 C 0 5.189 2.196 1.244 0.00 0.00 C+0
ATOM 25 O 0 3.791 0.042 0.696 0.00 0.00 O+0
ATOM 26 C 0 -0.036 -1.603 1.539 0.00 0.00 C+0
ATOM 27 C 0 1.274 -1.445 1.215 0.00 0.00 C+0
ATOM 28 C 0 2.265 -2.516 0.962 0.00 0.00 C+0
ATOM 29 C 0 2.666 -3.357 1.997 0.00 0.00 C+0
ATOM 30 C 0 3.590 -4.354 1.756 0.00 0.00 C+0
ATOM 31 C 0 4.122 -4.525 0.489 0.00 0.00 C+0
ATOM 32 C 0 3.735 -3.700 -0.548 0.00 0.00 C+0
ATOM 33 C 0 2.800 -2.693 -0.325 0.00 0.00 C+0
ATOM 34 C 0 2.381 -1.806 -1.435 0.00 0.00 C+0
ATOM 35 C 0 3.336 -1.099 -2.164 0.00 0.00 C+0
ATOM 36 C 0 2.941 -0.274 -3.197 0.00 0.00 C+0
ATOM 37 C 0 1.597 -0.146 -3.510 0.00 0.00 C+0
ATOM 38 F 0 1.215 0.663 -4.522 0.00 0.00 F+0
ATOM 39 C 0 0.644 -0.847 -2.788 0.00 0.00 C+0
ATOM 40 C 0 1.030 -1.679 -1.757 0.00 0.00 C+0
ATOM 41 H 0 -4.110 2.152 1.115 0.00 0.00 H+0
ATOM 42 H 0 -4.865 1.030 -0.798 0.00 0.00 H+0
ATOM 43 H 0 -4.987 -0.742 -0.687 0.00 0.00 H+0
ATOM 44 H 0 -6.621 2.263 0.145 0.00 0.00 H+0
ATOM 45 H 0 -7.287 1.007 -1.717 0.00 0.00 H+0
ATOM 46 H 0 -7.241 -0.764 -1.542 0.00 0.00 H+0
ATOM 47 H 0 -2.752 -0.961 0.192 0.00 0.00 H+0
ATOM 48 H 0 -2.465 0.795 0.145 0.00 0.00 H+0
ATOM 49 H 0 -2.086 0.798 2.596 0.00 0.00 H+0
ATOM 50 H 0 -2.373 -0.958 2.642 0.00 0.00 H+0
ATOM 51 H 0 0.130 1.659 1.537 0.00 0.00 H+0
ATOM 52 H 0 2.000 2.551 0.867 0.00 0.00 H+0
ATOM 53 H 0 3.228 4.232 -0.615 0.00 0.00 H+0
ATOM 54 H 0 5.385 5.380 -0.910 0.00 0.00 H+0
ATOM 55 H 0 7.412 4.491 0.166 0.00 0.00 H+0
ATOM 56 H 0 7.289 2.453 1.540 0.00 0.00 H+0
ATOM 57 H 0 5.136 1.301 1.847 0.00 0.00 H+0
ATOM 58 H 0 -0.546 -2.547 1.656 0.00 0.00 H+0
ATOM 59 H 0 2.256 -3.229 2.987 0.00 0.00 H+0
ATOM 60 H 0 3.900 -5.005 2.560 0.00 0.00 H+0
ATOM 61 H 0 4.845 -5.308 0.311 0.00 0.00 H+0
ATOM 62 H 0 4.154 -3.838 -1.534 0.00 0.00 H+0
ATOM 63 H 0 4.384 -1.197 -1.921 0.00 0.00 H+0
ATOM 64 H 0 3.681 0.274 -3.762 0.00 0.00 H+0
ATOM 65 H 0 -0.402 -0.744 -3.035 0.00 0.00 H+0
ATOM 66 H 0 0.286 -2.224 -1.195 0.00 0.00 H+0
CONECT 1 2 41 0 0 NONE 71
CONECT 2 1 3 4 12 NONE 72
CONECT 4 2 5 42 43 NONE 73
CONECT 5 4 6 7 8 NONE 74
CONECT 7 5 44 0 0 NONE 75
CONECT 8 5 9 45 46 NONE 76
CONECT 9 8 10 11 0 NONE 77
CONECT 10 9 0 0 0 NONE 78
CONECT 11 9 0 0 0 NONE 79
CONECT 12 2 13 47 48 NONE 80
CONECT 13 12 14 49 50 NONE 81
CONECT 14 13 15 26 0 NONE 82
CONECT 15 14 16 51 0 NONE 83
CONECT 16 15 27 17 0 NONE 84
CONECT 17 16 18 25 0 NONE 85
CONECT 18 17 19 52 0 NONE 86
CONECT 19 18 24 20 0 NONE 87
CONECT 20 19 21 53 0 NONE 88
CONECT 21 20 22 54 0 NONE 89
CONECT 22 21 23 55 0 NONE 90
CONECT 23 22 24 56 0 NONE 91
CONECT 24 23 19 57 0 NONE 92
CONECT 25 17 0 0 0 NONE 93
CONECT 26 14 27 58 0 NONE 94
CONECT 27 26 16 28 0 NONE 95
CONECT 28 27 33 29 0 NONE 96
CONECT 29 28 30 59 0 NONE 97
CONECT 30 29 31 60 0 NONE 98
CONECT 31 30 32 61 0 NONE 99
CONECT 32 31 33 62 0 NONE 100
CONECT 33 32 28 34 0 NONE 101
CONECT 34 33 40 35 0 NONE 102
CONECT 35 34 36 63 0 NONE 103
CONECT 36 35 37 64 0 NONE 104
CONECT 37 36 38 39 0 NONE 105
CONECT 38 37 0 0 0 NONE 106
CONECT 39 37 40 65 0 NONE 107
CONECT 40 39 34 66 0 NONE 108
END NONE 109
</inlineContents>
</jmolApplet>
</jmol>

==Usage & Indications==
lipitor can be used to prevent Cardiovascular Disease:
#Reduce the risk for revascularization procedures
#Reduce the risk of stroke
#Reduce the risk of myocardial infarction
It is indicated:
*as an adjunct to diet to reduce LDL-C, total-C, and apo B levels in postmenarchal girls and boys, about 10 to 17 years old.
*as an adjunct to diet for the treatment of patients with elevated serum TG levels.
*for the treatment of patients with primary dysbetalipoproteinemia who do not respond adequately to diet.

== Health Complication ==

Lipitor have been associated to some with muscle pain and Liver problems. The symptoms occuring due to these health issues includes muscle pain, feverlike symptoms, abdominal pain, fatique, or dark coloured urine

Lipitor can cause a number of side effect:[http://medguides.medicines.org.uk/displaypage.aspx?i=69&t=medicine side effect]
*allergic reaction
*loss of appetite
*bruising
*chest pain
*headache
*itching
*difficulty with memory/ thinking
*numbness in hand and feet

There have been numerous adverse side effect reports that lipitor could have been the cause of neuromuscular degeneration (losing control of muscle movement)[http://www.newmediaexplorer.org/sepp/2004/03/18/lipitor_side_effects_and_natural_remedy.htm 2]
Recent research shows that the grapefruit and lipitor could work.
Researchers have occasionally used grapefruit to boost the power of some expensive medications.
A man who breaks his Lipitor in half, takes it with grapefruit juice and gets good results on his cholesterol tests.

== Reference Link ==

*[http://www.lipitor.com/cwp/appmanager/lipitor/lipitorDesktop Lipitor Main Page]
*http://www.drugs.com/lipitor.html
*http://www.newmediaexplorer.org/sepp/2004/03/18/lipitor_side_effects_and_natural_remedy.htm
*http://organicdivision.org/essays_2001/schaus.pdf
*http://www.molecular-networks.com/online_demos/corina_demo.html
*http://www.rxlist.com/cgi/generic/atorvastatin_ids.htm
*http://www.dailypress.com/features/lifestyle/dp-85897sy0dec06,1,4716385.story?coll=dp-features-healthylife

It:Lipitor

2006-12-08T22:00:41Z

Rx104: /* Health Complication */

It:Lipitor

2006-12-08T21:52:39Z

Rx104: /* Reference Link */

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Systematic IUPAC Name
|-
| Systematic Iupac Name
| colspan="2"| [R-(R*, R*)]-2-(4-fluorophenyl)-beta,<br> delta-dihydroxy-5- <br>(1-methylethyl)-3-phenyl-4- <br>[(phenylamino)carbonyl]-1H-<br> pyrrole-1-heptanoic acid|-
|-
! {{chembox header}} colspan="3"| Identifiers
|-
| CAS registry number|CAS number
| colspan="2" | 134523-00-5
|-
| CAS registry number|ATC Code
| colspan="2" | C10AA05
|-
| CAS registry number|Pub Chem
| colspan="2" | 60823
|-
| CAS registry number|Drug Bank
| colspan="2" | APRD00055
|-
|-
! {{chembox header}} colspan="3"| Chemical Data
|-
| Chemical formula|Molecular formula
| colspan="2" | C<sub>33</sub>H<sub>34</sub>N<sub>2</sub>O<sub>5</sub>F
|-
| Molar mass
| colspan="2" | 558.64 g/mol
|-
! {{chembox header}} colspan="3"| Pharmacokinetic data
|-
| CAS registry number|Bioavailability
| colspan="2" | 15 %
|-
| CAS registry number|Metabolism
| colspan="2" | Liver
|-
| CAS registry number|Half Life
| colspan="2" | 14 Hours
|-
| CAS registry number|Excretion
| colspan="2" | Bile
|-
! {{chembox header}} colspan="3"| Therapeutic considerations
|-
| CAS registry number|Pregnancy Cat.
| colspan="2" | D(AU) X(US)
|-
| CAS registry number|Legal Status
| colspan="2" | S4(AU) POM(UK) ℞-only(US)
|-
| CAS registry number|Route
| colspan="2" | Oral

|}

Lipitor (Atorvastatin also a type of chiral drug) is a cholesterol-lowering medication (a type of HMG CoA reductase inhibitor) which belongs to a lass of medicine called statins. Lipitor is the most potent of all statins.It was introduced in 1996. It is used to block the production of cholesterol in the human body. Lipitor is also used to increase levels of HDL (good) cholesterol in the blood. This is important as it reduces the risk of hardening arteries which can lead to heart attacks, strokes and peripheral vascular disease.
[http://www.lipitor.com/cwp/appmanager/lipitor/lipitorDesktop 1]

Since 1996, Lipitor (lipitor marked jointly by Parke Davis and Pfizer, co-promoted by Warner-Lambert) had enormous growth in the international market of chiral drug. It has achieved sales up to $4 billion in 1999 (around 3 years of its market) which marked one of the best selling drug in US alone(41% of the US market). Lipitor has reached the worldwide market of cholesterol-reducing drug as the most potent drug in its class.

== How does it works ==

LDL (low density lipoprotein) cholesterol is not water soluble thus it travels in the human body in the form of lipoprotein. Once it reaches the human artery, it can cause a buildup of plaque in the lumen wall, constricting the blood flow, thus induces atherosclerosis (thickening of the arteries). Lipitor will competitively inhibit an enzyme in the liver (hepatic tissue) which is used to produce the LDL cholesterol.

== Synthesis ==
[[Image:atorvastatin synthesis.JPG]][http://organicdivision.org/essays_2001/schaus.pdf Synthesis]
<br>
An aldehyde is reacted with an enol ether to form alcohol '''15'''. The transesterification of the alcohol with NaOMe and methanol results in the methyl ester '''16'''. The enolate of tert-butylacetate ('''17''') is added to the methyl ester furthered by directed reduction to form the syn-1,3-diol '''18'''. The resultant is treated with NaOH in refluxing Toluene to form the cycled hydroxylactone '''19'''. Lastly, acid is used to 'open' the hydroxylactone thus forming a sodium salt which is treated with CaCl2.H2O to yield the atorvastatin (LIPITOR)
== Structure ==

[[Image:lipitor3.gif|centre|100|image produced in chemdraw]]

== 3D Structure ==

<jmol>
<jmolApplet>
<size>500</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
title1
title2
ATOM 1 O 0 -4.424 1.493 1.749 0.00 0.00 O+0
ATOM 2 C 0 -4.300 0.218 1.115 0.00 0.00 C+0
ATOM 3 H 0 -4.644 -0.561 1.796 0.00 0.00 H+0
ATOM 4 C 0 -5.150 0.196 -0.157 0.00 0.00 C+0
ATOM 5 C 0 -6.629 0.321 0.216 0.00 0.00 C+0
ATOM 6 H 0 -6.891 -0.462 0.928 0.00 0.00 H+0
ATOM 7 O 0 -6.865 1.601 0.806 0.00 0.00 O+0
ATOM 8 C 0 -7.486 0.174 -1.043 0.00 0.00 C+0
ATOM 9 C 0 -8.944 0.174 -0.661 0.00 0.00 C+0
ATOM 10 O 0 -9.267 0.281 0.510 0.00 0.00 O-1
ATOM 11 O 0 -9.800 0.066 -1.522 0.00 0.00 O+0
ATOM 12 C 0 -2.834 -0.031 0.753 0.00 0.00 C+0
ATOM 13 C 0 -2.003 -0.133 2.034 0.00 0.00 C+0
ATOM 14 N 0 -0.600 -0.372 1.688 0.00 0.00 N+0
ATOM 15 C 0 0.314 0.596 1.478 0.00 0.00 C+0
ATOM 16 C 0 1.511 0.010 1.177 0.00 0.00 C+0
ATOM 17 C 0 2.779 0.692 0.877 0.00 0.00 C+0
ATOM 18 N 0 2.820 2.037 0.803 0.00 0.00 N+0
ATOM 19 C 0 4.044 2.691 0.633 0.00 0.00 C+0
ATOM 20 C 0 4.117 3.842 -0.142 0.00 0.00 C+0
ATOM 21 C 0 5.328 4.485 -0.307 0.00 0.00 C+0
ATOM 22 C 0 6.467 3.986 0.297 0.00 0.00 C+0
ATOM 23 C 0 6.398 2.841 1.069 0.00 0.00 C+0
ATOM 24 C 0 5.189 2.196 1.244 0.00 0.00 C+0
ATOM 25 O 0 3.791 0.042 0.696 0.00 0.00 O+0
ATOM 26 C 0 -0.036 -1.603 1.539 0.00 0.00 C+0
ATOM 27 C 0 1.274 -1.445 1.215 0.00 0.00 C+0
ATOM 28 C 0 2.265 -2.516 0.962 0.00 0.00 C+0
ATOM 29 C 0 2.666 -3.357 1.997 0.00 0.00 C+0
ATOM 30 C 0 3.590 -4.354 1.756 0.00 0.00 C+0
ATOM 31 C 0 4.122 -4.525 0.489 0.00 0.00 C+0
ATOM 32 C 0 3.735 -3.700 -0.548 0.00 0.00 C+0
ATOM 33 C 0 2.800 -2.693 -0.325 0.00 0.00 C+0
ATOM 34 C 0 2.381 -1.806 -1.435 0.00 0.00 C+0
ATOM 35 C 0 3.336 -1.099 -2.164 0.00 0.00 C+0
ATOM 36 C 0 2.941 -0.274 -3.197 0.00 0.00 C+0
ATOM 37 C 0 1.597 -0.146 -3.510 0.00 0.00 C+0
ATOM 38 F 0 1.215 0.663 -4.522 0.00 0.00 F+0
ATOM 39 C 0 0.644 -0.847 -2.788 0.00 0.00 C+0
ATOM 40 C 0 1.030 -1.679 -1.757 0.00 0.00 C+0
ATOM 41 H 0 -4.110 2.152 1.115 0.00 0.00 H+0
ATOM 42 H 0 -4.865 1.030 -0.798 0.00 0.00 H+0
ATOM 43 H 0 -4.987 -0.742 -0.687 0.00 0.00 H+0
ATOM 44 H 0 -6.621 2.263 0.145 0.00 0.00 H+0
ATOM 45 H 0 -7.287 1.007 -1.717 0.00 0.00 H+0
ATOM 46 H 0 -7.241 -0.764 -1.542 0.00 0.00 H+0
ATOM 47 H 0 -2.752 -0.961 0.192 0.00 0.00 H+0
ATOM 48 H 0 -2.465 0.795 0.145 0.00 0.00 H+0
ATOM 49 H 0 -2.086 0.798 2.596 0.00 0.00 H+0
ATOM 50 H 0 -2.373 -0.958 2.642 0.00 0.00 H+0
ATOM 51 H 0 0.130 1.659 1.537 0.00 0.00 H+0
ATOM 52 H 0 2.000 2.551 0.867 0.00 0.00 H+0
ATOM 53 H 0 3.228 4.232 -0.615 0.00 0.00 H+0
ATOM 54 H 0 5.385 5.380 -0.910 0.00 0.00 H+0
ATOM 55 H 0 7.412 4.491 0.166 0.00 0.00 H+0
ATOM 56 H 0 7.289 2.453 1.540 0.00 0.00 H+0
ATOM 57 H 0 5.136 1.301 1.847 0.00 0.00 H+0
ATOM 58 H 0 -0.546 -2.547 1.656 0.00 0.00 H+0
ATOM 59 H 0 2.256 -3.229 2.987 0.00 0.00 H+0
ATOM 60 H 0 3.900 -5.005 2.560 0.00 0.00 H+0
ATOM 61 H 0 4.845 -5.308 0.311 0.00 0.00 H+0
ATOM 62 H 0 4.154 -3.838 -1.534 0.00 0.00 H+0
ATOM 63 H 0 4.384 -1.197 -1.921 0.00 0.00 H+0
ATOM 64 H 0 3.681 0.274 -3.762 0.00 0.00 H+0
ATOM 65 H 0 -0.402 -0.744 -3.035 0.00 0.00 H+0
ATOM 66 H 0 0.286 -2.224 -1.195 0.00 0.00 H+0
CONECT 1 2 41 0 0 NONE 71
CONECT 2 1 3 4 12 NONE 72
CONECT 4 2 5 42 43 NONE 73
CONECT 5 4 6 7 8 NONE 74
CONECT 7 5 44 0 0 NONE 75
CONECT 8 5 9 45 46 NONE 76
CONECT 9 8 10 11 0 NONE 77
CONECT 10 9 0 0 0 NONE 78
CONECT 11 9 0 0 0 NONE 79
CONECT 12 2 13 47 48 NONE 80
CONECT 13 12 14 49 50 NONE 81
CONECT 14 13 15 26 0 NONE 82
CONECT 15 14 16 51 0 NONE 83
CONECT 16 15 27 17 0 NONE 84
CONECT 17 16 18 25 0 NONE 85
CONECT 18 17 19 52 0 NONE 86
CONECT 19 18 24 20 0 NONE 87
CONECT 20 19 21 53 0 NONE 88
CONECT 21 20 22 54 0 NONE 89
CONECT 22 21 23 55 0 NONE 90
CONECT 23 22 24 56 0 NONE 91
CONECT 24 23 19 57 0 NONE 92
CONECT 25 17 0 0 0 NONE 93
CONECT 26 14 27 58 0 NONE 94
CONECT 27 26 16 28 0 NONE 95
CONECT 28 27 33 29 0 NONE 96
CONECT 29 28 30 59 0 NONE 97
CONECT 30 29 31 60 0 NONE 98
CONECT 31 30 32 61 0 NONE 99
CONECT 32 31 33 62 0 NONE 100
CONECT 33 32 28 34 0 NONE 101
CONECT 34 33 40 35 0 NONE 102
CONECT 35 34 36 63 0 NONE 103
CONECT 36 35 37 64 0 NONE 104
CONECT 37 36 38 39 0 NONE 105
CONECT 38 37 0 0 0 NONE 106
CONECT 39 37 40 65 0 NONE 107
CONECT 40 39 34 66 0 NONE 108
END NONE 109
</inlineContents>
</jmolApplet>
</jmol>

==Usage & Indications==
lipitor can be used to prevent Cardiovascular Disease:
#Reduce the risk for revascularization procedures
#Reduce the risk of stroke
#Reduce the risk of myocardial infarction
It is indicated:
*as an adjunct to diet to reduce LDL-C, total-C, and apo B levels in postmenarchal girls and boys, about 10 to 17 years old.
*as an adjunct to diet for the treatment of patients with elevated serum TG levels.
*for the treatment of patients with primary dysbetalipoproteinemia who do not respond adequately to diet.

== Health Complication ==

Lipitor have been associated to some with muscle pain and Liver problems. The symptoms occuring due to these health issues includes muscle pain, feverlike symptoms, abdominal pain, fatique, or dark coloured urine

Lipitor can cause a number of side effect:[http://medguides.medicines.org.uk/displaypage.aspx?i=69&t=medicine side effect]
*allergic reaction
*loss of appetite
*bruising
*chest pain
*headache
*itching
*difficulty with memory/ thinking
*numbness in hand and feet

There have been numerous adverse side effect reports that lipitor could have been the cause of neuromuscular degeneration (losing control of muscle movement)[http://www.newmediaexplorer.org/sepp/2004/03/18/lipitor_side_effects_and_natural_remedy.htm 2]

== Reference Link ==

*[http://www.lipitor.com/cwp/appmanager/lipitor/lipitorDesktop Lipitor Main Page]
*http://www.drugs.com/lipitor.html
*http://www.newmediaexplorer.org/sepp/2004/03/18/lipitor_side_effects_and_natural_remedy.htm
*http://organicdivision.org/essays_2001/schaus.pdf
*http://www.molecular-networks.com/online_demos/corina_demo.html
*http://www.rxlist.com/cgi/generic/atorvastatin_ids.htm

It:Lipitor

2006-12-08T21:51:49Z

Rx104: /* Usage & Indications */

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Systematic IUPAC Name
|-
| Systematic Iupac Name
| colspan="2"| [R-(R*, R*)]-2-(4-fluorophenyl)-beta,<br> delta-dihydroxy-5- <br>(1-methylethyl)-3-phenyl-4- <br>[(phenylamino)carbonyl]-1H-<br> pyrrole-1-heptanoic acid|-
|-
! {{chembox header}} colspan="3"| Identifiers
|-
| CAS registry number|CAS number
| colspan="2" | 134523-00-5
|-
| CAS registry number|ATC Code
| colspan="2" | C10AA05
|-
| CAS registry number|Pub Chem
| colspan="2" | 60823
|-
| CAS registry number|Drug Bank
| colspan="2" | APRD00055
|-
|-
! {{chembox header}} colspan="3"| Chemical Data
|-
| Chemical formula|Molecular formula
| colspan="2" | C<sub>33</sub>H<sub>34</sub>N<sub>2</sub>O<sub>5</sub>F
|-
| Molar mass
| colspan="2" | 558.64 g/mol
|-
! {{chembox header}} colspan="3"| Pharmacokinetic data
|-
| CAS registry number|Bioavailability
| colspan="2" | 15 %
|-
| CAS registry number|Metabolism
| colspan="2" | Liver
|-
| CAS registry number|Half Life
| colspan="2" | 14 Hours
|-
| CAS registry number|Excretion
| colspan="2" | Bile
|-
! {{chembox header}} colspan="3"| Therapeutic considerations
|-
| CAS registry number|Pregnancy Cat.
| colspan="2" | D(AU) X(US)
|-
| CAS registry number|Legal Status
| colspan="2" | S4(AU) POM(UK) ℞-only(US)
|-
| CAS registry number|Route
| colspan="2" | Oral

|}

Lipitor (Atorvastatin also a type of chiral drug) is a cholesterol-lowering medication (a type of HMG CoA reductase inhibitor) which belongs to a lass of medicine called statins. Lipitor is the most potent of all statins.It was introduced in 1996. It is used to block the production of cholesterol in the human body. Lipitor is also used to increase levels of HDL (good) cholesterol in the blood. This is important as it reduces the risk of hardening arteries which can lead to heart attacks, strokes and peripheral vascular disease.
[http://www.lipitor.com/cwp/appmanager/lipitor/lipitorDesktop 1]

Since 1996, Lipitor (lipitor marked jointly by Parke Davis and Pfizer, co-promoted by Warner-Lambert) had enormous growth in the international market of chiral drug. It has achieved sales up to $4 billion in 1999 (around 3 years of its market) which marked one of the best selling drug in US alone(41% of the US market). Lipitor has reached the worldwide market of cholesterol-reducing drug as the most potent drug in its class.

== How does it works ==

LDL (low density lipoprotein) cholesterol is not water soluble thus it travels in the human body in the form of lipoprotein. Once it reaches the human artery, it can cause a buildup of plaque in the lumen wall, constricting the blood flow, thus induces atherosclerosis (thickening of the arteries). Lipitor will competitively inhibit an enzyme in the liver (hepatic tissue) which is used to produce the LDL cholesterol.

== Synthesis ==
[[Image:atorvastatin synthesis.JPG]][http://organicdivision.org/essays_2001/schaus.pdf Synthesis]
<br>
An aldehyde is reacted with an enol ether to form alcohol '''15'''. The transesterification of the alcohol with NaOMe and methanol results in the methyl ester '''16'''. The enolate of tert-butylacetate ('''17''') is added to the methyl ester furthered by directed reduction to form the syn-1,3-diol '''18'''. The resultant is treated with NaOH in refluxing Toluene to form the cycled hydroxylactone '''19'''. Lastly, acid is used to 'open' the hydroxylactone thus forming a sodium salt which is treated with CaCl2.H2O to yield the atorvastatin (LIPITOR)
== Structure ==

[[Image:lipitor3.gif|centre|100|image produced in chemdraw]]

== 3D Structure ==

<jmol>
<jmolApplet>
<size>500</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
title1
title2
ATOM 1 O 0 -4.424 1.493 1.749 0.00 0.00 O+0
ATOM 2 C 0 -4.300 0.218 1.115 0.00 0.00 C+0
ATOM 3 H 0 -4.644 -0.561 1.796 0.00 0.00 H+0
ATOM 4 C 0 -5.150 0.196 -0.157 0.00 0.00 C+0
ATOM 5 C 0 -6.629 0.321 0.216 0.00 0.00 C+0
ATOM 6 H 0 -6.891 -0.462 0.928 0.00 0.00 H+0
ATOM 7 O 0 -6.865 1.601 0.806 0.00 0.00 O+0
ATOM 8 C 0 -7.486 0.174 -1.043 0.00 0.00 C+0
ATOM 9 C 0 -8.944 0.174 -0.661 0.00 0.00 C+0
ATOM 10 O 0 -9.267 0.281 0.510 0.00 0.00 O-1
ATOM 11 O 0 -9.800 0.066 -1.522 0.00 0.00 O+0
ATOM 12 C 0 -2.834 -0.031 0.753 0.00 0.00 C+0
ATOM 13 C 0 -2.003 -0.133 2.034 0.00 0.00 C+0
ATOM 14 N 0 -0.600 -0.372 1.688 0.00 0.00 N+0
ATOM 15 C 0 0.314 0.596 1.478 0.00 0.00 C+0
ATOM 16 C 0 1.511 0.010 1.177 0.00 0.00 C+0
ATOM 17 C 0 2.779 0.692 0.877 0.00 0.00 C+0
ATOM 18 N 0 2.820 2.037 0.803 0.00 0.00 N+0
ATOM 19 C 0 4.044 2.691 0.633 0.00 0.00 C+0
ATOM 20 C 0 4.117 3.842 -0.142 0.00 0.00 C+0
ATOM 21 C 0 5.328 4.485 -0.307 0.00 0.00 C+0
ATOM 22 C 0 6.467 3.986 0.297 0.00 0.00 C+0
ATOM 23 C 0 6.398 2.841 1.069 0.00 0.00 C+0
ATOM 24 C 0 5.189 2.196 1.244 0.00 0.00 C+0
ATOM 25 O 0 3.791 0.042 0.696 0.00 0.00 O+0
ATOM 26 C 0 -0.036 -1.603 1.539 0.00 0.00 C+0
ATOM 27 C 0 1.274 -1.445 1.215 0.00 0.00 C+0
ATOM 28 C 0 2.265 -2.516 0.962 0.00 0.00 C+0
ATOM 29 C 0 2.666 -3.357 1.997 0.00 0.00 C+0
ATOM 30 C 0 3.590 -4.354 1.756 0.00 0.00 C+0
ATOM 31 C 0 4.122 -4.525 0.489 0.00 0.00 C+0
ATOM 32 C 0 3.735 -3.700 -0.548 0.00 0.00 C+0
ATOM 33 C 0 2.800 -2.693 -0.325 0.00 0.00 C+0
ATOM 34 C 0 2.381 -1.806 -1.435 0.00 0.00 C+0
ATOM 35 C 0 3.336 -1.099 -2.164 0.00 0.00 C+0
ATOM 36 C 0 2.941 -0.274 -3.197 0.00 0.00 C+0
ATOM 37 C 0 1.597 -0.146 -3.510 0.00 0.00 C+0
ATOM 38 F 0 1.215 0.663 -4.522 0.00 0.00 F+0
ATOM 39 C 0 0.644 -0.847 -2.788 0.00 0.00 C+0
ATOM 40 C 0 1.030 -1.679 -1.757 0.00 0.00 C+0
ATOM 41 H 0 -4.110 2.152 1.115 0.00 0.00 H+0
ATOM 42 H 0 -4.865 1.030 -0.798 0.00 0.00 H+0
ATOM 43 H 0 -4.987 -0.742 -0.687 0.00 0.00 H+0
ATOM 44 H 0 -6.621 2.263 0.145 0.00 0.00 H+0
ATOM 45 H 0 -7.287 1.007 -1.717 0.00 0.00 H+0
ATOM 46 H 0 -7.241 -0.764 -1.542 0.00 0.00 H+0
ATOM 47 H 0 -2.752 -0.961 0.192 0.00 0.00 H+0
ATOM 48 H 0 -2.465 0.795 0.145 0.00 0.00 H+0
ATOM 49 H 0 -2.086 0.798 2.596 0.00 0.00 H+0
ATOM 50 H 0 -2.373 -0.958 2.642 0.00 0.00 H+0
ATOM 51 H 0 0.130 1.659 1.537 0.00 0.00 H+0
ATOM 52 H 0 2.000 2.551 0.867 0.00 0.00 H+0
ATOM 53 H 0 3.228 4.232 -0.615 0.00 0.00 H+0
ATOM 54 H 0 5.385 5.380 -0.910 0.00 0.00 H+0
ATOM 55 H 0 7.412 4.491 0.166 0.00 0.00 H+0
ATOM 56 H 0 7.289 2.453 1.540 0.00 0.00 H+0
ATOM 57 H 0 5.136 1.301 1.847 0.00 0.00 H+0
ATOM 58 H 0 -0.546 -2.547 1.656 0.00 0.00 H+0
ATOM 59 H 0 2.256 -3.229 2.987 0.00 0.00 H+0
ATOM 60 H 0 3.900 -5.005 2.560 0.00 0.00 H+0
ATOM 61 H 0 4.845 -5.308 0.311 0.00 0.00 H+0
ATOM 62 H 0 4.154 -3.838 -1.534 0.00 0.00 H+0
ATOM 63 H 0 4.384 -1.197 -1.921 0.00 0.00 H+0
ATOM 64 H 0 3.681 0.274 -3.762 0.00 0.00 H+0
ATOM 65 H 0 -0.402 -0.744 -3.035 0.00 0.00 H+0
ATOM 66 H 0 0.286 -2.224 -1.195 0.00 0.00 H+0
CONECT 1 2 41 0 0 NONE 71
CONECT 2 1 3 4 12 NONE 72
CONECT 4 2 5 42 43 NONE 73
CONECT 5 4 6 7 8 NONE 74
CONECT 7 5 44 0 0 NONE 75
CONECT 8 5 9 45 46 NONE 76
CONECT 9 8 10 11 0 NONE 77
CONECT 10 9 0 0 0 NONE 78
CONECT 11 9 0 0 0 NONE 79
CONECT 12 2 13 47 48 NONE 80
CONECT 13 12 14 49 50 NONE 81
CONECT 14 13 15 26 0 NONE 82
CONECT 15 14 16 51 0 NONE 83
CONECT 16 15 27 17 0 NONE 84
CONECT 17 16 18 25 0 NONE 85
CONECT 18 17 19 52 0 NONE 86
CONECT 19 18 24 20 0 NONE 87
CONECT 20 19 21 53 0 NONE 88
CONECT 21 20 22 54 0 NONE 89
CONECT 22 21 23 55 0 NONE 90
CONECT 23 22 24 56 0 NONE 91
CONECT 24 23 19 57 0 NONE 92
CONECT 25 17 0 0 0 NONE 93
CONECT 26 14 27 58 0 NONE 94
CONECT 27 26 16 28 0 NONE 95
CONECT 28 27 33 29 0 NONE 96
CONECT 29 28 30 59 0 NONE 97
CONECT 30 29 31 60 0 NONE 98
CONECT 31 30 32 61 0 NONE 99
CONECT 32 31 33 62 0 NONE 100
CONECT 33 32 28 34 0 NONE 101
CONECT 34 33 40 35 0 NONE 102
CONECT 35 34 36 63 0 NONE 103
CONECT 36 35 37 64 0 NONE 104
CONECT 37 36 38 39 0 NONE 105
CONECT 38 37 0 0 0 NONE 106
CONECT 39 37 40 65 0 NONE 107
CONECT 40 39 34 66 0 NONE 108
END NONE 109
</inlineContents>
</jmolApplet>
</jmol>

==Usage & Indications==
lipitor can be used to prevent Cardiovascular Disease:
#Reduce the risk for revascularization procedures
#Reduce the risk of stroke
#Reduce the risk of myocardial infarction
It is indicated:
*as an adjunct to diet to reduce LDL-C, total-C, and apo B levels in postmenarchal girls and boys, about 10 to 17 years old.
*as an adjunct to diet for the treatment of patients with elevated serum TG levels.
*for the treatment of patients with primary dysbetalipoproteinemia who do not respond adequately to diet.

== Health Complication ==

Lipitor have been associated to some with muscle pain and Liver problems. The symptoms occuring due to these health issues includes muscle pain, feverlike symptoms, abdominal pain, fatique, or dark coloured urine

Lipitor can cause a number of side effect:[http://medguides.medicines.org.uk/displaypage.aspx?i=69&t=medicine side effect]
*allergic reaction
*loss of appetite
*bruising
*chest pain
*headache
*itching
*difficulty with memory/ thinking
*numbness in hand and feet

There have been numerous adverse side effect reports that lipitor could have been the cause of neuromuscular degeneration (losing control of muscle movement)[http://www.newmediaexplorer.org/sepp/2004/03/18/lipitor_side_effects_and_natural_remedy.htm 2]

== Reference Link ==

*[http://www.lipitor.com/cwp/appmanager/lipitor/lipitorDesktop Lipitor Main Page]
*http://www.drugs.com/lipitor.html
*http://www.newmediaexplorer.org/sepp/2004/03/18/lipitor_side_effects_and_natural_remedy.htm
*http://organicdivision.org/essays_2001/schaus.pdf
*http://www.molecular-networks.com/online_demos/corina_demo.html

It:Lipitor

2006-12-08T21:51:00Z

Rx104: /* Health Complication */

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Systematic IUPAC Name
|-
| Systematic Iupac Name
| colspan="2"| [R-(R*, R*)]-2-(4-fluorophenyl)-beta,<br> delta-dihydroxy-5- <br>(1-methylethyl)-3-phenyl-4- <br>[(phenylamino)carbonyl]-1H-<br> pyrrole-1-heptanoic acid|-
|-
! {{chembox header}} colspan="3"| Identifiers
|-
| CAS registry number|CAS number
| colspan="2" | 134523-00-5
|-
| CAS registry number|ATC Code
| colspan="2" | C10AA05
|-
| CAS registry number|Pub Chem
| colspan="2" | 60823
|-
| CAS registry number|Drug Bank
| colspan="2" | APRD00055
|-
|-
! {{chembox header}} colspan="3"| Chemical Data
|-
| Chemical formula|Molecular formula
| colspan="2" | C<sub>33</sub>H<sub>34</sub>N<sub>2</sub>O<sub>5</sub>F
|-
| Molar mass
| colspan="2" | 558.64 g/mol
|-
! {{chembox header}} colspan="3"| Pharmacokinetic data
|-
| CAS registry number|Bioavailability
| colspan="2" | 15 %
|-
| CAS registry number|Metabolism
| colspan="2" | Liver
|-
| CAS registry number|Half Life
| colspan="2" | 14 Hours
|-
| CAS registry number|Excretion
| colspan="2" | Bile
|-
! {{chembox header}} colspan="3"| Therapeutic considerations
|-
| CAS registry number|Pregnancy Cat.
| colspan="2" | D(AU) X(US)
|-
| CAS registry number|Legal Status
| colspan="2" | S4(AU) POM(UK) ℞-only(US)
|-
| CAS registry number|Route
| colspan="2" | Oral

|}

Lipitor (Atorvastatin also a type of chiral drug) is a cholesterol-lowering medication (a type of HMG CoA reductase inhibitor) which belongs to a lass of medicine called statins. Lipitor is the most potent of all statins.It was introduced in 1996. It is used to block the production of cholesterol in the human body. Lipitor is also used to increase levels of HDL (good) cholesterol in the blood. This is important as it reduces the risk of hardening arteries which can lead to heart attacks, strokes and peripheral vascular disease.
[http://www.lipitor.com/cwp/appmanager/lipitor/lipitorDesktop 1]

Since 1996, Lipitor (lipitor marked jointly by Parke Davis and Pfizer, co-promoted by Warner-Lambert) had enormous growth in the international market of chiral drug. It has achieved sales up to $4 billion in 1999 (around 3 years of its market) which marked one of the best selling drug in US alone(41% of the US market). Lipitor has reached the worldwide market of cholesterol-reducing drug as the most potent drug in its class.

== How does it works ==

LDL (low density lipoprotein) cholesterol is not water soluble thus it travels in the human body in the form of lipoprotein. Once it reaches the human artery, it can cause a buildup of plaque in the lumen wall, constricting the blood flow, thus induces atherosclerosis (thickening of the arteries). Lipitor will competitively inhibit an enzyme in the liver (hepatic tissue) which is used to produce the LDL cholesterol.

== Synthesis ==
[[Image:atorvastatin synthesis.JPG]][http://organicdivision.org/essays_2001/schaus.pdf Synthesis]
<br>
An aldehyde is reacted with an enol ether to form alcohol '''15'''. The transesterification of the alcohol with NaOMe and methanol results in the methyl ester '''16'''. The enolate of tert-butylacetate ('''17''') is added to the methyl ester furthered by directed reduction to form the syn-1,3-diol '''18'''. The resultant is treated with NaOH in refluxing Toluene to form the cycled hydroxylactone '''19'''. Lastly, acid is used to 'open' the hydroxylactone thus forming a sodium salt which is treated with CaCl2.H2O to yield the atorvastatin (LIPITOR)
== Structure ==

[[Image:lipitor3.gif|centre|100|image produced in chemdraw]]

== 3D Structure ==

<jmol>
<jmolApplet>
<size>500</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
title1
title2
ATOM 1 O 0 -4.424 1.493 1.749 0.00 0.00 O+0
ATOM 2 C 0 -4.300 0.218 1.115 0.00 0.00 C+0
ATOM 3 H 0 -4.644 -0.561 1.796 0.00 0.00 H+0
ATOM 4 C 0 -5.150 0.196 -0.157 0.00 0.00 C+0
ATOM 5 C 0 -6.629 0.321 0.216 0.00 0.00 C+0
ATOM 6 H 0 -6.891 -0.462 0.928 0.00 0.00 H+0
ATOM 7 O 0 -6.865 1.601 0.806 0.00 0.00 O+0
ATOM 8 C 0 -7.486 0.174 -1.043 0.00 0.00 C+0
ATOM 9 C 0 -8.944 0.174 -0.661 0.00 0.00 C+0
ATOM 10 O 0 -9.267 0.281 0.510 0.00 0.00 O-1
ATOM 11 O 0 -9.800 0.066 -1.522 0.00 0.00 O+0
ATOM 12 C 0 -2.834 -0.031 0.753 0.00 0.00 C+0
ATOM 13 C 0 -2.003 -0.133 2.034 0.00 0.00 C+0
ATOM 14 N 0 -0.600 -0.372 1.688 0.00 0.00 N+0
ATOM 15 C 0 0.314 0.596 1.478 0.00 0.00 C+0
ATOM 16 C 0 1.511 0.010 1.177 0.00 0.00 C+0
ATOM 17 C 0 2.779 0.692 0.877 0.00 0.00 C+0
ATOM 18 N 0 2.820 2.037 0.803 0.00 0.00 N+0
ATOM 19 C 0 4.044 2.691 0.633 0.00 0.00 C+0
ATOM 20 C 0 4.117 3.842 -0.142 0.00 0.00 C+0
ATOM 21 C 0 5.328 4.485 -0.307 0.00 0.00 C+0
ATOM 22 C 0 6.467 3.986 0.297 0.00 0.00 C+0
ATOM 23 C 0 6.398 2.841 1.069 0.00 0.00 C+0
ATOM 24 C 0 5.189 2.196 1.244 0.00 0.00 C+0
ATOM 25 O 0 3.791 0.042 0.696 0.00 0.00 O+0
ATOM 26 C 0 -0.036 -1.603 1.539 0.00 0.00 C+0
ATOM 27 C 0 1.274 -1.445 1.215 0.00 0.00 C+0
ATOM 28 C 0 2.265 -2.516 0.962 0.00 0.00 C+0
ATOM 29 C 0 2.666 -3.357 1.997 0.00 0.00 C+0
ATOM 30 C 0 3.590 -4.354 1.756 0.00 0.00 C+0
ATOM 31 C 0 4.122 -4.525 0.489 0.00 0.00 C+0
ATOM 32 C 0 3.735 -3.700 -0.548 0.00 0.00 C+0
ATOM 33 C 0 2.800 -2.693 -0.325 0.00 0.00 C+0
ATOM 34 C 0 2.381 -1.806 -1.435 0.00 0.00 C+0
ATOM 35 C 0 3.336 -1.099 -2.164 0.00 0.00 C+0
ATOM 36 C 0 2.941 -0.274 -3.197 0.00 0.00 C+0
ATOM 37 C 0 1.597 -0.146 -3.510 0.00 0.00 C+0
ATOM 38 F 0 1.215 0.663 -4.522 0.00 0.00 F+0
ATOM 39 C 0 0.644 -0.847 -2.788 0.00 0.00 C+0
ATOM 40 C 0 1.030 -1.679 -1.757 0.00 0.00 C+0
ATOM 41 H 0 -4.110 2.152 1.115 0.00 0.00 H+0
ATOM 42 H 0 -4.865 1.030 -0.798 0.00 0.00 H+0
ATOM 43 H 0 -4.987 -0.742 -0.687 0.00 0.00 H+0
ATOM 44 H 0 -6.621 2.263 0.145 0.00 0.00 H+0
ATOM 45 H 0 -7.287 1.007 -1.717 0.00 0.00 H+0
ATOM 46 H 0 -7.241 -0.764 -1.542 0.00 0.00 H+0
ATOM 47 H 0 -2.752 -0.961 0.192 0.00 0.00 H+0
ATOM 48 H 0 -2.465 0.795 0.145 0.00 0.00 H+0
ATOM 49 H 0 -2.086 0.798 2.596 0.00 0.00 H+0
ATOM 50 H 0 -2.373 -0.958 2.642 0.00 0.00 H+0
ATOM 51 H 0 0.130 1.659 1.537 0.00 0.00 H+0
ATOM 52 H 0 2.000 2.551 0.867 0.00 0.00 H+0
ATOM 53 H 0 3.228 4.232 -0.615 0.00 0.00 H+0
ATOM 54 H 0 5.385 5.380 -0.910 0.00 0.00 H+0
ATOM 55 H 0 7.412 4.491 0.166 0.00 0.00 H+0
ATOM 56 H 0 7.289 2.453 1.540 0.00 0.00 H+0
ATOM 57 H 0 5.136 1.301 1.847 0.00 0.00 H+0
ATOM 58 H 0 -0.546 -2.547 1.656 0.00 0.00 H+0
ATOM 59 H 0 2.256 -3.229 2.987 0.00 0.00 H+0
ATOM 60 H 0 3.900 -5.005 2.560 0.00 0.00 H+0
ATOM 61 H 0 4.845 -5.308 0.311 0.00 0.00 H+0
ATOM 62 H 0 4.154 -3.838 -1.534 0.00 0.00 H+0
ATOM 63 H 0 4.384 -1.197 -1.921 0.00 0.00 H+0
ATOM 64 H 0 3.681 0.274 -3.762 0.00 0.00 H+0
ATOM 65 H 0 -0.402 -0.744 -3.035 0.00 0.00 H+0
ATOM 66 H 0 0.286 -2.224 -1.195 0.00 0.00 H+0
CONECT 1 2 41 0 0 NONE 71
CONECT 2 1 3 4 12 NONE 72
CONECT 4 2 5 42 43 NONE 73
CONECT 5 4 6 7 8 NONE 74
CONECT 7 5 44 0 0 NONE 75
CONECT 8 5 9 45 46 NONE 76
CONECT 9 8 10 11 0 NONE 77
CONECT 10 9 0 0 0 NONE 78
CONECT 11 9 0 0 0 NONE 79
CONECT 12 2 13 47 48 NONE 80
CONECT 13 12 14 49 50 NONE 81
CONECT 14 13 15 26 0 NONE 82
CONECT 15 14 16 51 0 NONE 83
CONECT 16 15 27 17 0 NONE 84
CONECT 17 16 18 25 0 NONE 85
CONECT 18 17 19 52 0 NONE 86
CONECT 19 18 24 20 0 NONE 87
CONECT 20 19 21 53 0 NONE 88
CONECT 21 20 22 54 0 NONE 89
CONECT 22 21 23 55 0 NONE 90
CONECT 23 22 24 56 0 NONE 91
CONECT 24 23 19 57 0 NONE 92
CONECT 25 17 0 0 0 NONE 93
CONECT 26 14 27 58 0 NONE 94
CONECT 27 26 16 28 0 NONE 95
CONECT 28 27 33 29 0 NONE 96
CONECT 29 28 30 59 0 NONE 97
CONECT 30 29 31 60 0 NONE 98
CONECT 31 30 32 61 0 NONE 99
CONECT 32 31 33 62 0 NONE 100
CONECT 33 32 28 34 0 NONE 101
CONECT 34 33 40 35 0 NONE 102
CONECT 35 34 36 63 0 NONE 103
CONECT 36 35 37 64 0 NONE 104
CONECT 37 36 38 39 0 NONE 105
CONECT 38 37 0 0 0 NONE 106
CONECT 39 37 40 65 0 NONE 107
CONECT 40 39 34 66 0 NONE 108
END NONE 109
</inlineContents>
</jmolApplet>
</jmol>

==Usage & Indications==
lipitor can be used to prevent Cardiovascular Disease:
#Reduce the risk for revascularization procedures
#Reduce the risk of stroke
#Reduce the risk of myocardial infarction
It is indicated:
*as an adjunct to diet to reduce LDL-C, total-C, and apo B levels in postmenarchal girls and boys, about 10 to 17 years old.
*as an adjunct to diet for the treatment of patients with elevated serum TG levels.
*for the treatment of patients with primary dysbetalipoproteinemia who do not respond adequately to diet.

== Health Complication ==

Lipitor have been associated to some with muscle pain and Liver problems. The symptoms occuring due to these health issues includes muscle pain, feverlike symptoms, abdominal pain, fatique, or dark coloured urine

Lipitor can cause a number of side effect:[http://medguides.medicines.org.uk/displaypage.aspx?i=69&t=medicine side effect]
*allergic reaction
*loss of appetite
*bruising
*chest pain
*headache
*itching
*difficulty with memory/ thinking
*numbness in hand and feet

There have been numerous adverse side effect reports that lipitor could have been the cause of neuromuscular degeneration (losing control of muscle movement)[http://www.newmediaexplorer.org/sepp/2004/03/18/lipitor_side_effects_and_natural_remedy.htm 2]

== Reference Link ==

*[http://www.lipitor.com/cwp/appmanager/lipitor/lipitorDesktop Lipitor Main Page]
*http://www.drugs.com/lipitor.html
*http://www.newmediaexplorer.org/sepp/2004/03/18/lipitor_side_effects_and_natural_remedy.htm
*http://organicdivision.org/essays_2001/schaus.pdf
*http://www.molecular-networks.com/online_demos/corina_demo.html

It:Cyameluric Acid

2006-12-08T21:26:37Z

Rx104: /* References */

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |2D Structure of Cyanmeluric Acid
|-
| align="center" colspan="3" bgcolour="#ffffff" | [[Image:Cyanmeluric Acid jaa05.gif]]
|-
! {{chembox header}} colspan="3" |3D structure of Cyanmeluric Acid<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER NONAME 20-Nov-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 20-Nov-06 0 NONE 4
ATOM 1 O 0 -1.758 -3.611 0.001 0.00 0.00 O-1
ATOM 2 C 0 -1.166 -2.396 0.001 0.00 0.00 C+0
ATOM 3 N 0 0.161 -2.322 0.000 0.00 0.00 N+0
ATOM 4 C 0 0.766 -1.134 0.000 0.00 0.00 C+0
ATOM 5 N 0 0.000 0.000 0.000 0.00 0.00 N+0
ATOM 6 N 0 2.094 -1.016 -0.000 0.00 0.00 N+0
ATOM 7 C 0 2.658 0.188 -0.000 0.00 0.00 C+0
ATOM 8 O 0 4.006 0.283 -0.000 0.00 0.00 O-1
ATOM 9 N 0 1.930 1.300 -0.000 0.00 0.00 N+0
ATOM 10 C 0 0.599 1.231 0.001 0.00 0.00 C+0
ATOM 11 N 0 -0.167 2.321 -0.000 0.00 0.00 N+0
ATOM 12 C 0 -1.492 2.208 0.001 0.00 0.00 C+0
ATOM 13 O 0 -2.248 3.328 -0.000 0.00 0.00 O-1
ATOM 14 N 0 -2.091 1.021 0.001 0.00 0.00 N+0
ATOM 15 C 0 -1.366 -0.097 0.000 0.00 0.00 C+0
ATOM 16 N 0 -1.927 -1.305 -0.004 0.00 0.00 N+0
CONECT 1 2 0 0 0 NONE 21
CONECT 2 1 16 3 0 NONE 22
CONECT 3 2 4 0 0 NONE 23
CONECT 4 3 5 6 0 NONE 24
CONECT 5 4 10 15 0 NONE 25
CONECT 6 4 7 0 0 NONE 26
CONECT 7 6 8 9 0 NONE 27
CONECT 8 7 0 0 0 NONE 28
CONECT 9 7 10 0 0 NONE 29
CONECT 10 9 5 11 0 NONE 30
CONECT 11 10 12 0 0 NONE 31
CONECT 12 11 13 14 0 NONE 32
CONECT 13 12 0 0 0 NONE 33
CONECT 14 12 15 0 0 NONE 34
CONECT 15 14 5 16 0 NONE 35
CONECT 16 15 2 0 0 NONE 36
END NONE 37
</inlineContents>
</jmolApplet>
</jmol>
|-
! {{chembox header}} colspan="3" | Properties
|-
| colspan="1" |IUPAC Systematic Name
| colspan="2"|
|-
| colspan="1" |CA Index Name
| colspan="2" |1,3,4,6,7,9,9b-Heptaazaphenalene-2,5,8(1H,3H,6H)
-trione, tripotassium salt, hydrate (9CI)
|-
| colspan="1" |Other Names
| colspan="2" |Cyameluric acid, tripotassium salt, hydrate
|-
| colspan="1" |Molecular formula
| colspan="2" |C<sub>6</sub>N<sub>7</sub>O<sub>3</sub><sup>3-</sup>
|-
| colspan="1" |SMILES String
| colspan="2" |[O-]C1=NC(N23)=NC([O-])=NC2=NC([O-])=NC3=N1
|-
| colspan="1" |Molecular Mass
| colspan="2" |218.11
|-
| colspan="1" |Appearance
| colspan="2" |
|-
|colspan="1" |Beilstein Registry number
| colspan="2" |3842474
|-
| colspan="1" |CAS Registry Number
| colspan="2" |42431-24-3
|-
| Melting Point
| colspan="2" |
|-
|colspan="1" |Boiling point
| colspan="2" |
|-
|colspan="1" |Refractive index
| colspan="2" |

|}

==History==
[[Image:Heptazines.bmp]]

The compound show above is called tri-s-triazine or 1,3,4,6,7,9,9b-Heptaazaphenalene or cyamelurine, if we change three R group with three amino substituents it is called melem. In Melon the heptazine is polymerized with the tri-s-triazine units linked through an amine (NH) link.

Derivate of heptazine with three hydroxyl substituents is called Cyameluric acid. The first person to suggest a structure for cyameluric acid is Josef Loschmidt, at 1861. His structure is in fact a meta-cyclophane, but this at a time when cyclic compounds of any type were not widely recognised.

==Discovery of Cyameluric acid==
Cyameluric acid is discovered in 1850, this compound continued to baffle until 1937.Pauling proposed an entirely different structure from Loschmidt's imaginative meta-cyclophane structure .
http://www.ch.ic.ac.uk/rzepa/loschmidt/loschmidt-Pages/Image1.html
The cyameluric acid is insoluble both in organic solvents and water. Gives neither melting point or boiling point.It is inert, only can under go hydrolytic cleavage.
In 1937 a structure of '''cyameluric acid''', C<sub>6</sub>N<sub>7</sub>(OH)<sub>3</sub>, was proposed by ''Pauling'' and ''Sturdivant''. The structure differed greatly from those of previous scientists. This type of molecule seemed to fascinate Pauling; the last thing he wrote on the chalkboard in his office before his death in 1994 was an azide derivative of cyameluric acid. It has been preserved there to this day by his friends.

In 1850 Henneberg prepared salts of the acid, and in 1933 Professor E. C. Franklin suggested the structure:

[[Image:Franklin.bmp]]

Franklin's research led Pauling and Sturdivant to similar formulations as studied by Franklin; hydromelonic acid is related to cyameluric acid as cyanuric tricyanamide is to cyanuric acid.

The Pauling/Sturdivant structure for cyameluric acid is made up of 3 coplanar rings fused together, with all angles approximately equal to 120°, the structure of the cyamelurate ion is shown in the table on the right. It is a delocalised system, and can be represented in a similar way to ''Kekule's'' structure for benzene, in a conjugated form:

[[Image:Resonance.bmp]]

Infinite structures can be formed in a hydrogen bonding network.

This proposed structure seems to hold the best explanation of properties of cyameluric acid. The resonance forms account for the high stability and the acid strength. This structure also corresponds to the hydrolysis porducts and is therefore the most likely structure. Although there is no report of the crystal structure of cyameluric acid to date.

==Tautomeric==

As cyameluric acid has seventeen tautomers, which is the most stable one?
The seventeen tautomers of Cyameluric acid is showed below:

[[Image:Tautomeric1.jpg]]

[[Image:Tautomeric2.JPG]]

[[Image:Table 1.JPG]]

DFT calculations (B3LYP/6-31G*) have been carried out on the these tautomers and find out the C3h trioxo tautomer 258 is the most stable. Some energies and absolute NMR shieldings (GIAO) were calculated for 258 and other tri-s-triazines, including cyamelurine and Pauling mystery molecule.

== Tips==
The heptazine derivate with an azide substituent and two hydroxyl groups is called Linus Pauling's mystery molecule. Two theories attempt to lift the mystery. It is suggested that Pauling failed to solve the double helix structure of DNA before Watson and Crick because he viewed uracil as an amide and not as the tautomeric hydroxy compound. The other theory suggests that Pauling intented to use the compound as a potential spectroscopic label for binding to DNA.

==References==

1. [http://www.arkat-usa.org/ARKIVOC/JOURNAL_CONTENT/manuscripts/2004/EM-917KP%20as%20published%20mainmanuscript.pdf "Theroetical study of cyameluric acid and related compounds"]

2. ''Proceedings of the National Academy of Sciences of the Untied States of America'', Vol. 23, No. 12, pp. 615-620 : '''The Structure of Cyameluric Acid, Hydromelonic Acid, and Related Substance''' - Linus Pauling; J. H. Sturdivant

3. [http://en.wikipedia.org/wiki/Melem''Melem'']

4.http://pubs.acs.org/cgi-bin/archive.cgi/jacsat/1939/61/i12/pdf/ja01267a056.pdf

5.http://www.ch.ic.ac.uk/rzepa/loschmidt/

It:Cyameluric Acid

2006-12-08T21:26:15Z

Rx104: /* References */

It:Cyameluric Acid

2006-12-08T21:25:38Z

Rx104: /* Discovery of Cyameluric acid */

It:Cyameluric Acid

2006-12-08T21:01:21Z

Rx104: /* References */

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |2D Structure of Cyanmeluric Acid
|-
| align="center" colspan="3" bgcolour="#ffffff" | [[Image:Cyanmeluric Acid jaa05.gif]]
|-
! {{chembox header}} colspan="3" |3D structure of Cyanmeluric Acid<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER NONAME 20-Nov-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 20-Nov-06 0 NONE 4
ATOM 1 O 0 -1.758 -3.611 0.001 0.00 0.00 O-1
ATOM 2 C 0 -1.166 -2.396 0.001 0.00 0.00 C+0
ATOM 3 N 0 0.161 -2.322 0.000 0.00 0.00 N+0
ATOM 4 C 0 0.766 -1.134 0.000 0.00 0.00 C+0
ATOM 5 N 0 0.000 0.000 0.000 0.00 0.00 N+0
ATOM 6 N 0 2.094 -1.016 -0.000 0.00 0.00 N+0
ATOM 7 C 0 2.658 0.188 -0.000 0.00 0.00 C+0
ATOM 8 O 0 4.006 0.283 -0.000 0.00 0.00 O-1
ATOM 9 N 0 1.930 1.300 -0.000 0.00 0.00 N+0
ATOM 10 C 0 0.599 1.231 0.001 0.00 0.00 C+0
ATOM 11 N 0 -0.167 2.321 -0.000 0.00 0.00 N+0
ATOM 12 C 0 -1.492 2.208 0.001 0.00 0.00 C+0
ATOM 13 O 0 -2.248 3.328 -0.000 0.00 0.00 O-1
ATOM 14 N 0 -2.091 1.021 0.001 0.00 0.00 N+0
ATOM 15 C 0 -1.366 -0.097 0.000 0.00 0.00 C+0
ATOM 16 N 0 -1.927 -1.305 -0.004 0.00 0.00 N+0
CONECT 1 2 0 0 0 NONE 21
CONECT 2 1 16 3 0 NONE 22
CONECT 3 2 4 0 0 NONE 23
CONECT 4 3 5 6 0 NONE 24
CONECT 5 4 10 15 0 NONE 25
CONECT 6 4 7 0 0 NONE 26
CONECT 7 6 8 9 0 NONE 27
CONECT 8 7 0 0 0 NONE 28
CONECT 9 7 10 0 0 NONE 29
CONECT 10 9 5 11 0 NONE 30
CONECT 11 10 12 0 0 NONE 31
CONECT 12 11 13 14 0 NONE 32
CONECT 13 12 0 0 0 NONE 33
CONECT 14 12 15 0 0 NONE 34
CONECT 15 14 5 16 0 NONE 35
CONECT 16 15 2 0 0 NONE 36
END NONE 37
</inlineContents>
</jmolApplet>
</jmol>
|-
! {{chembox header}} colspan="3" | Properties
|-
| colspan="1" |IUPAC Systematic Name
| colspan="2"|
|-
| colspan="1" |CA Index Name
| colspan="2" |1,3,4,6,7,9,9b-Heptaazaphenalene-2,5,8(1H,3H,6H)
-trione, tripotassium salt, hydrate (9CI)
|-
| colspan="1" |Other Names
| colspan="2" |Cyameluric acid, tripotassium salt, hydrate
|-
| colspan="1" |Molecular formula
| colspan="2" |C<sub>6</sub>N<sub>7</sub>O<sub>3</sub><sup>3-</sup>
|-
| colspan="1" |SMILES String
| colspan="2" |[O-]C1=NC(N23)=NC([O-])=NC2=NC([O-])=NC3=N1
|-
| colspan="1" |Molecular Mass
| colspan="2" |218.11
|-
| colspan="1" |Appearance
| colspan="2" |
|-
|colspan="1" |Beilstein Registry number
| colspan="2" |3842474
|-
| colspan="1" |CAS Registry Number
| colspan="2" |42431-24-3
|-
| Melting Point
| colspan="2" |
|-
|colspan="1" |Boiling point
| colspan="2" |
|-
|colspan="1" |Refractive index
| colspan="2" |

|}

==History==
[[Image:Heptazines.bmp]]

The compound show above is called tri-s-triazine or 1,3,4,6,7,9,9b-Heptaazaphenalene or cyamelurine, if we change three R group with three amino substituents it is called melem. In Melon the heptazine is polymerized with the tri-s-triazine units linked through an amine (NH) link.

Derivate of heptazine with three hydroxyl substituents is called Cyameluric acid. The first person to suggest a structure for cyameluric acid is Josef Loschmidt, at 1861. His structure is in fact a meta-cyclophane, but this at a time when cyclic compounds of any type were not widely recognised.

==Discovery of Cyameluric acid==
The cyameluric acid is insoluble both in organic solvents and water. Gives neither melting point or boiling point.It is inert, only can under go hydrolytic cleavage.
In 1937 a structure of '''cyameluric acid''', C<sub>6</sub>N<sub>7</sub>(OH)<sub>3</sub>, was proposed by ''Pauling'' and ''Sturdivant''. The structure differed greatly from those of previous scientists. This type of molecule seemed to fascinate Pauling; the last thing he wrote on the chalkboard in his office before his death in 1994 was an azide derivative of cyameluric acid. It has been preserved there to this day by his friends.

In 1850 Henneberg prepared salts of the acid, and in 1933 Professor E. C. Franklin suggested the structure:

[[Image:Franklin.bmp]]

Franklin's research led Pauling and Sturdivant to similar formulations as studied by Franklin; hydromelonic acid is related to cyameluric acid as cyanuric tricyanamide is to cyanuric acid.

The Pauling/Sturdivant structure for cyameluric acid is made up of 3 coplanar rings fused together, with all angles approximately equal to 120°, the structure of the cyamelurate ion is shown in the table on the right. It is a delocalised system, and can be represented in a similar way to ''Kekule's'' structure for benzene, in a conjugated form:

[[Image:Resonance.bmp]]

Infinite structures can be formed in a hydrogen bonding network.

This proposed structure seems to hold the best explanation of properties of cyameluric acid. The resonance forms account for the high stability and the acid strength. This structure also corresponds to the hydrolysis porducts and is therefore the most likely structure. Although there is no report of the crystal structure of cyameluric acid to date.

==Tautomeric==

As cyameluric acid has seventeen tautomers, which is the most stable one?
The seventeen tautomers of Cyameluric acid is showed below:

[[Image:Tautomeric1.jpg]]

[[Image:Tautomeric2.JPG]]

[[Image:Table 1.JPG]]

DFT calculations (B3LYP/6-31G*) have been carried out on the these tautomers and find out the C3h trioxo tautomer 258 is the most stable. Some energies and absolute NMR shieldings (GIAO) were calculated for 258 and other tri-s-triazines, including cyamelurine and Pauling mystery molecule.

== Tips==
The heptazine derivate with an azide substituent and two hydroxyl groups is called Linus Pauling's mystery molecule. Two theories attempt to lift the mystery. It is suggested that Pauling failed to solve the double helix structure of DNA before Watson and Crick because he viewed uracil as an amide and not as the tautomeric hydroxy compound. The other theory suggests that Pauling intented to use the compound as a potential spectroscopic label for binding to DNA.

==References==

1. [http://www.arkat-usa.org/ARKIVOC/JOURNAL_CONTENT/manuscripts/2004/EM-917KP%20as%20published%20mainmanuscript.pdf "Theroetical study of cyameluric acid and related compounds"]

2. ''Proceedings of the National Academy of Sciences of the Untied States of America'', Vol. 23, No. 12, pp. 615-620 : '''The Structure of Cyameluric Acid, Hydromelonic Acid, and Related Substance''' - Linus Pauling; J. H. Sturdivant

3. [http://en.wikipedia.org/wiki/Melem''Melem'']

4.http://pubs.acs.org/cgi-bin/archive.cgi/jacsat/1939/61/i12/pdf/ja01267a056.pdf

It:Cyameluric Acid

2006-12-08T21:00:58Z

Rx104: /* References */

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |2D Structure of Cyanmeluric Acid
|-
| align="center" colspan="3" bgcolour="#ffffff" | [[Image:Cyanmeluric Acid jaa05.gif]]
|-
! {{chembox header}} colspan="3" |3D structure of Cyanmeluric Acid<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER NONAME 20-Nov-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 20-Nov-06 0 NONE 4
ATOM 1 O 0 -1.758 -3.611 0.001 0.00 0.00 O-1
ATOM 2 C 0 -1.166 -2.396 0.001 0.00 0.00 C+0
ATOM 3 N 0 0.161 -2.322 0.000 0.00 0.00 N+0
ATOM 4 C 0 0.766 -1.134 0.000 0.00 0.00 C+0
ATOM 5 N 0 0.000 0.000 0.000 0.00 0.00 N+0
ATOM 6 N 0 2.094 -1.016 -0.000 0.00 0.00 N+0
ATOM 7 C 0 2.658 0.188 -0.000 0.00 0.00 C+0
ATOM 8 O 0 4.006 0.283 -0.000 0.00 0.00 O-1
ATOM 9 N 0 1.930 1.300 -0.000 0.00 0.00 N+0
ATOM 10 C 0 0.599 1.231 0.001 0.00 0.00 C+0
ATOM 11 N 0 -0.167 2.321 -0.000 0.00 0.00 N+0
ATOM 12 C 0 -1.492 2.208 0.001 0.00 0.00 C+0
ATOM 13 O 0 -2.248 3.328 -0.000 0.00 0.00 O-1
ATOM 14 N 0 -2.091 1.021 0.001 0.00 0.00 N+0
ATOM 15 C 0 -1.366 -0.097 0.000 0.00 0.00 C+0
ATOM 16 N 0 -1.927 -1.305 -0.004 0.00 0.00 N+0
CONECT 1 2 0 0 0 NONE 21
CONECT 2 1 16 3 0 NONE 22
CONECT 3 2 4 0 0 NONE 23
CONECT 4 3 5 6 0 NONE 24
CONECT 5 4 10 15 0 NONE 25
CONECT 6 4 7 0 0 NONE 26
CONECT 7 6 8 9 0 NONE 27
CONECT 8 7 0 0 0 NONE 28
CONECT 9 7 10 0 0 NONE 29
CONECT 10 9 5 11 0 NONE 30
CONECT 11 10 12 0 0 NONE 31
CONECT 12 11 13 14 0 NONE 32
CONECT 13 12 0 0 0 NONE 33
CONECT 14 12 15 0 0 NONE 34
CONECT 15 14 5 16 0 NONE 35
CONECT 16 15 2 0 0 NONE 36
END NONE 37
</inlineContents>
</jmolApplet>
</jmol>
|-
! {{chembox header}} colspan="3" | Properties
|-
| colspan="1" |IUPAC Systematic Name
| colspan="2"|
|-
| colspan="1" |CA Index Name
| colspan="2" |1,3,4,6,7,9,9b-Heptaazaphenalene-2,5,8(1H,3H,6H)
-trione, tripotassium salt, hydrate (9CI)
|-
| colspan="1" |Other Names
| colspan="2" |Cyameluric acid, tripotassium salt, hydrate
|-
| colspan="1" |Molecular formula
| colspan="2" |C<sub>6</sub>N<sub>7</sub>O<sub>3</sub><sup>3-</sup>
|-
| colspan="1" |SMILES String
| colspan="2" |[O-]C1=NC(N23)=NC([O-])=NC2=NC([O-])=NC3=N1
|-
| colspan="1" |Molecular Mass
| colspan="2" |218.11
|-
| colspan="1" |Appearance
| colspan="2" |
|-
|colspan="1" |Beilstein Registry number
| colspan="2" |3842474
|-
| colspan="1" |CAS Registry Number
| colspan="2" |42431-24-3
|-
| Melting Point
| colspan="2" |
|-
|colspan="1" |Boiling point
| colspan="2" |
|-
|colspan="1" |Refractive index
| colspan="2" |

|}

==History==
[[Image:Heptazines.bmp]]

The compound show above is called tri-s-triazine or 1,3,4,6,7,9,9b-Heptaazaphenalene or cyamelurine, if we change three R group with three amino substituents it is called melem. In Melon the heptazine is polymerized with the tri-s-triazine units linked through an amine (NH) link.

Derivate of heptazine with three hydroxyl substituents is called Cyameluric acid. The first person to suggest a structure for cyameluric acid is Josef Loschmidt, at 1861. His structure is in fact a meta-cyclophane, but this at a time when cyclic compounds of any type were not widely recognised.

==Discovery of Cyameluric acid==
The cyameluric acid is insoluble both in organic solvents and water. Gives neither melting point or boiling point.It is inert, only can under go hydrolytic cleavage.
In 1937 a structure of '''cyameluric acid''', C<sub>6</sub>N<sub>7</sub>(OH)<sub>3</sub>, was proposed by ''Pauling'' and ''Sturdivant''. The structure differed greatly from those of previous scientists. This type of molecule seemed to fascinate Pauling; the last thing he wrote on the chalkboard in his office before his death in 1994 was an azide derivative of cyameluric acid. It has been preserved there to this day by his friends.

In 1850 Henneberg prepared salts of the acid, and in 1933 Professor E. C. Franklin suggested the structure:

[[Image:Franklin.bmp]]

Franklin's research led Pauling and Sturdivant to similar formulations as studied by Franklin; hydromelonic acid is related to cyameluric acid as cyanuric tricyanamide is to cyanuric acid.

The Pauling/Sturdivant structure for cyameluric acid is made up of 3 coplanar rings fused together, with all angles approximately equal to 120°, the structure of the cyamelurate ion is shown in the table on the right. It is a delocalised system, and can be represented in a similar way to ''Kekule's'' structure for benzene, in a conjugated form:

[[Image:Resonance.bmp]]

Infinite structures can be formed in a hydrogen bonding network.

This proposed structure seems to hold the best explanation of properties of cyameluric acid. The resonance forms account for the high stability and the acid strength. This structure also corresponds to the hydrolysis porducts and is therefore the most likely structure. Although there is no report of the crystal structure of cyameluric acid to date.

==Tautomeric==

As cyameluric acid has seventeen tautomers, which is the most stable one?
The seventeen tautomers of Cyameluric acid is showed below:

[[Image:Tautomeric1.jpg]]

[[Image:Tautomeric2.JPG]]

[[Image:Table 1.JPG]]

DFT calculations (B3LYP/6-31G*) have been carried out on the these tautomers and find out the C3h trioxo tautomer 258 is the most stable. Some energies and absolute NMR shieldings (GIAO) were calculated for 258 and other tri-s-triazines, including cyamelurine and Pauling mystery molecule.

== Tips==
The heptazine derivate with an azide substituent and two hydroxyl groups is called Linus Pauling's mystery molecule. Two theories attempt to lift the mystery. It is suggested that Pauling failed to solve the double helix structure of DNA before Watson and Crick because he viewed uracil as an amide and not as the tautomeric hydroxy compound. The other theory suggests that Pauling intented to use the compound as a potential spectroscopic label for binding to DNA.

==References==

1. [http://www.arkat-usa.org/ARKIVOC/JOURNAL_CONTENT/manuscripts/2004/EM-917KP%20as%20published%20mainmanuscript.pdf "Theroetical study of cyameluric acid and related compounds"]

2. ''Proceedings of the National Academy of Sciences of the Untied States of America'', Vol. 23, No. 12, pp. 615-620 : '''The Structure of Cyameluric Acid, Hydromelonic Acid, and Related Substance''' - Linus Pauling; J. H. Sturdivant

3. [http://en.wikipedia.org/wiki/Melem''Melem'']

4.[http://pubs.acs.org/cgi-bin/archive.cgi/jacsat/1939/61/i12/pdf/ja01267a056.pdf]

It:Cyameluric Acid

2006-12-08T20:52:28Z

Rx104: /* Discovery of Cyameluric acid */

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |2D Structure of Cyanmeluric Acid
|-
| align="center" colspan="3" bgcolour="#ffffff" | [[Image:Cyanmeluric Acid jaa05.gif]]
|-
! {{chembox header}} colspan="3" |3D structure of Cyanmeluric Acid<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER NONAME 20-Nov-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 20-Nov-06 0 NONE 4
ATOM 1 O 0 -1.758 -3.611 0.001 0.00 0.00 O-1
ATOM 2 C 0 -1.166 -2.396 0.001 0.00 0.00 C+0
ATOM 3 N 0 0.161 -2.322 0.000 0.00 0.00 N+0
ATOM 4 C 0 0.766 -1.134 0.000 0.00 0.00 C+0
ATOM 5 N 0 0.000 0.000 0.000 0.00 0.00 N+0
ATOM 6 N 0 2.094 -1.016 -0.000 0.00 0.00 N+0
ATOM 7 C 0 2.658 0.188 -0.000 0.00 0.00 C+0
ATOM 8 O 0 4.006 0.283 -0.000 0.00 0.00 O-1
ATOM 9 N 0 1.930 1.300 -0.000 0.00 0.00 N+0
ATOM 10 C 0 0.599 1.231 0.001 0.00 0.00 C+0
ATOM 11 N 0 -0.167 2.321 -0.000 0.00 0.00 N+0
ATOM 12 C 0 -1.492 2.208 0.001 0.00 0.00 C+0
ATOM 13 O 0 -2.248 3.328 -0.000 0.00 0.00 O-1
ATOM 14 N 0 -2.091 1.021 0.001 0.00 0.00 N+0
ATOM 15 C 0 -1.366 -0.097 0.000 0.00 0.00 C+0
ATOM 16 N 0 -1.927 -1.305 -0.004 0.00 0.00 N+0
CONECT 1 2 0 0 0 NONE 21
CONECT 2 1 16 3 0 NONE 22
CONECT 3 2 4 0 0 NONE 23
CONECT 4 3 5 6 0 NONE 24
CONECT 5 4 10 15 0 NONE 25
CONECT 6 4 7 0 0 NONE 26
CONECT 7 6 8 9 0 NONE 27
CONECT 8 7 0 0 0 NONE 28
CONECT 9 7 10 0 0 NONE 29
CONECT 10 9 5 11 0 NONE 30
CONECT 11 10 12 0 0 NONE 31
CONECT 12 11 13 14 0 NONE 32
CONECT 13 12 0 0 0 NONE 33
CONECT 14 12 15 0 0 NONE 34
CONECT 15 14 5 16 0 NONE 35
CONECT 16 15 2 0 0 NONE 36
END NONE 37
</inlineContents>
</jmolApplet>
</jmol>
|-
! {{chembox header}} colspan="3" | Properties
|-
| colspan="1" |IUPAC Systematic Name
| colspan="2"|
|-
| colspan="1" |CA Index Name
| colspan="2" |1,3,4,6,7,9,9b-Heptaazaphenalene-2,5,8(1H,3H,6H)
-trione, tripotassium salt, hydrate (9CI)
|-
| colspan="1" |Other Names
| colspan="2" |Cyameluric acid, tripotassium salt, hydrate
|-
| colspan="1" |Molecular formula
| colspan="2" |C<sub>6</sub>N<sub>7</sub>O<sub>3</sub><sup>3-</sup>
|-
| colspan="1" |SMILES String
| colspan="2" |[O-]C1=NC(N23)=NC([O-])=NC2=NC([O-])=NC3=N1
|-
| colspan="1" |Molecular Mass
| colspan="2" |218.11
|-
| colspan="1" |Appearance
| colspan="2" |
|-
|colspan="1" |Beilstein Registry number
| colspan="2" |3842474
|-
| colspan="1" |CAS Registry Number
| colspan="2" |42431-24-3
|-
| Melting Point
| colspan="2" |
|-
|colspan="1" |Boiling point
| colspan="2" |
|-
|colspan="1" |Refractive index
| colspan="2" |

|}

==History==
[[Image:Heptazines.bmp]]

The compound show above is called tri-s-triazine or 1,3,4,6,7,9,9b-Heptaazaphenalene or cyamelurine, if we change three R group with three amino substituents it is called melem. In Melon the heptazine is polymerized with the tri-s-triazine units linked through an amine (NH) link.

Derivate of heptazine with three hydroxyl substituents is called Cyameluric acid. The first person to suggest a structure for cyameluric acid is Josef Loschmidt, at 1861. His structure is in fact a meta-cyclophane, but this at a time when cyclic compounds of any type were not widely recognised.

==Discovery of Cyameluric acid==
The cyameluric acid is insoluble both in organic solvents and water. Gives neither melting point or boiling point.It is inert, only can under go hydrolytic cleavage.
In 1937 a structure of '''cyameluric acid''', C<sub>6</sub>N<sub>7</sub>(OH)<sub>3</sub>, was proposed by ''Pauling'' and ''Sturdivant''. The structure differed greatly from those of previous scientists. This type of molecule seemed to fascinate Pauling; the last thing he wrote on the chalkboard in his office before his death in 1994 was an azide derivative of cyameluric acid. It has been preserved there to this day by his friends.

In 1850 Henneberg prepared salts of the acid, and in 1933 Professor E. C. Franklin suggested the structure:

[[Image:Franklin.bmp]]

Franklin's research led Pauling and Sturdivant to similar formulations as studied by Franklin; hydromelonic acid is related to cyameluric acid as cyanuric tricyanamide is to cyanuric acid.

The Pauling/Sturdivant structure for cyameluric acid is made up of 3 coplanar rings fused together, with all angles approximately equal to 120°, the structure of the cyamelurate ion is shown in the table on the right. It is a delocalised system, and can be represented in a similar way to ''Kekule's'' structure for benzene, in a conjugated form:

[[Image:Resonance.bmp]]

Infinite structures can be formed in a hydrogen bonding network.

This proposed structure seems to hold the best explanation of properties of cyameluric acid. The resonance forms account for the high stability and the acid strength. This structure also corresponds to the hydrolysis porducts and is therefore the most likely structure. Although there is no report of the crystal structure of cyameluric acid to date.

==Tautomeric==

As cyameluric acid has seventeen tautomers, which is the most stable one?
The seventeen tautomers of Cyameluric acid is showed below:

[[Image:Tautomeric1.jpg]]

[[Image:Tautomeric2.JPG]]

[[Image:Table 1.JPG]]

DFT calculations (B3LYP/6-31G*) have been carried out on the these tautomers and find out the C3h trioxo tautomer 258 is the most stable. Some energies and absolute NMR shieldings (GIAO) were calculated for 258 and other tri-s-triazines, including cyamelurine and Pauling mystery molecule.

== Tips==
The heptazine derivate with an azide substituent and two hydroxyl groups is called Linus Pauling's mystery molecule. Two theories attempt to lift the mystery. It is suggested that Pauling failed to solve the double helix structure of DNA before Watson and Crick because he viewed uracil as an amide and not as the tautomeric hydroxy compound. The other theory suggests that Pauling intented to use the compound as a potential spectroscopic label for binding to DNA.

==References==

1. [http://www.arkat-usa.org/ARKIVOC/JOURNAL_CONTENT/manuscripts/2004/EM-917KP%20as%20published%20mainmanuscript.pdf "Theroetical study of cyameluric acid and related compounds"]

2. ''Proceedings of the National Academy of Sciences of the Untied States of America'', Vol. 23, No. 12, pp. 615-620 : '''The Structure of Cyameluric Acid, Hydromelonic Acid, and Related Substance''' - Linus Pauling; J. H. Sturdivant

3. [http://en.wikipedia.org/wiki/Melem''Melem'']