Benzylpiperazine (BZP) is a stimulant used recreationally. It is the key ingredient of "party pills" which are taken by people desiring a burst of energy, often so they can keep active during long raves and parties.

==3D structure==

<jmol>
<jmolApplet>
<size>325</size>
<color>white</color>
<script>zoom 100; cpk off;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>HEADER CSD ENTRY XICKAV
ATOM 1 C1 MOL 1 13.908 12.651 -0.170 1.00 0.00
ATOM 2 C2 MOL 1 12.549 11.954 -0.045 1.00 0.00
ATOM 3 N3 MOL 1 15.088 11.818 0.193 1.00 0.00
ATOM 4 C4 MOL 1 11.455 12.621 -0.420 1.00 0.00
ATOM 5 C5 MOL 1 12.403 10.590 0.503 1.00 0.00
ATOM 6 C6 MOL 1 16.268 12.703 0.271 1.00 0.00
ATOM 7 C7 MOL 1 15.357 10.768 -0.829 1.00 0.00
ATOM 8 C8 MOL 1 10.132 12.004 -0.300 1.00 0.00
ATOM 9 C9 MOL 1 11.200 10.031 0.607 1.00 0.00
ATOM 10 C10 MOL 1 17.504 11.884 0.696 1.00 0.00
ATOM 11 C11 MOL 1 16.584 9.939 -0.396 1.00 0.00
ATOM 12 C12 MOL 1 10.010 10.771 0.187 1.00 0.00
ATOM 13 N13 MOL 1 17.757 10.824 -0.294 1.00 0.00
ATOM 14 H28 MOL 1 14.018 12.945 -1.119 1.00 0.00
ATOM 15 H30 MOL 1 13.900 13.452 0.429 1.00 0.00
ATOM 16 H32 MOL 1 11.540 13.548 -0.786 1.00 0.00
ATOM 17 H34 MOL 1 13.214 10.083 0.798 1.00 0.00
ATOM 18 H36 MOL 1 16.434 13.115 -0.625 1.00 0.00
ATOM 19 H38 MOL 1 16.099 13.423 0.944 1.00 0.00
ATOM 20 H40 MOL 1 14.561 10.169 -0.910 1.00 0.00
ATOM 21 H42 MOL 1 15.541 11.200 -1.712 1.00 0.00
ATOM 22 H44 MOL 1 9.318 12.510 -0.585 1.00 0.00
ATOM 23 H46 MOL 1 11.109 9.104 0.973 1.00 0.00
ATOM 24 H48 MOL 1 18.300 12.487 0.748 1.00 0.00
ATOM 25 H50 MOL 1 17.339 11.471 1.591 1.00 0.00
ATOM 26 H52 MOL 1 16.405 9.517 0.493 1.00 0.00
ATOM 27 H54 MOL 1 16.761 9.225 -1.074 1.00 0.00
ATOM 28 H56 MOL 1 9.105 10.351 0.265 1.00 0.00
ATOM 29 H58 MOL 1 17.936 11.239 -1.186 1.00 0.00
END</inlineContents>
</jmolApplet>
</jmol>

==Synthesis of Benzylpiperazine==
[[Image:Benzylpiperazinesy.png]]
[http://designer-drug.com/pte/12.162.180.114/dcd/chemistry/bzp.html Synthesis_of_Benzylpiperazine]

It:Benzylpiperazine

2006-11-27T11:57:44Z

Gld04:

2006-11-27T10:49:19Z

Gld04:

It:Benzylpiperazine

2006-11-27T10:46:58Z

Gld04:

Gld04:

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}}| '''Vioxx (treatment of osteoarthritis symptoms and pain)'''

|-
| align="center" colspan="2" bgcolor="#ffffff" |[[Image:Vioxx2.png]]
|-
| [[IUPAC nomenclature|Chemical name]]
| ''12(5H)-Furanone,

4-[4-(methylsulfonyl)phenyl]-3-phenyl- (9CI)''
|-
| [[Other names]]
| 3-(4-Methanesulfonylphenyl)-2-phenyl-2-buten-4-olide;

3-Phenyl-4-[4-(Methylsulfonyl)phenyl]-2(5H)-furanone;

4-(4-(Methanesulfonyl)phenyl)-3-phenyl-5H-furan-2-one;

4-[(4-Methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone;

MK 0966; MK 966; Rofecoxib; Vioxx
|-
| [[CAS nummber]]
| 162011-90-7
|-
| [[Chemical formula]]
| C17 H14 O4 S
|-
| [[Molecular mass]]
| {{{mol_mass|314.355768 g/mol
|-
| Melting point
| 207°C[http://www.chemblink.com/products/162011-90-7.htm (m)]
|-
| [[H2O Solubility]]
| Insoluble
|-
| [[State]]
| Solid
|-
| [[Drug Category]]
| Anti-Inflammatory Agents,

Non-Steroidal

Cyclooxygenase Inhibitors
|-
| [[Indication]]
| For the treatment of osteoarthritis,

acute pain in adults and menstrual pain.
|-
| [[Toxicity]]
| No overdoses of rofecoxib were reported

during clinical trials. Administration of

single doses of rofecoxib 1000 mg to 6 healthy

volunteers and multiple doses of 250 mg/day

for 14 days to 75 healthy volunteers did not

result in serious toxicity.
|-
| [[Protein Binding]]
| 87%
|-
| [[Half Life]]
| 17 Hours
|-
| And here is a 3D picture:[http://redpoll.pharmacy.ualberta.ca/drugbank/drugBank/drugPDB_unzipped/APRD00151_PDB.txt (1)]
|
<jmol>
<jmolApplet>
<size>325</size>
<color>silver</color>
<script>zoom 125; cpk off;frame 1; move 100 -100 100 0 0 0 0 0 2; delay 1;</script>
<inlineContents>water.mol
title1
title2

ATOM 1 C 0 5.085 1.062 0.967 0.00 0.00 C+0
ATOM 2 S 0 4.266 -0.246 0.015 0.00 0.00 S+0
ATOM 3 O 0 4.606 -0.182 -1.363 0.00 0.00 O+0
ATOM 4 O 0 4.236 -1.474 0.729 0.00 0.00 O+0
ATOM 5 C 0 2.575 0.250 0.023 0.00 0.00 C+0
ATOM 6 C 0 2.093 1.068 -0.985 0.00 0.00 C+0
ATOM 7 C 0 0.772 1.461 -0.986 0.00 0.00 C+0
ATOM 8 C 0 -0.083 1.031 0.035 0.00 0.00 C+0
ATOM 9 C 0 0.412 0.204 1.050 0.00 0.00 C+0
ATOM 10 C 0 1.735 -0.184 1.033 0.00 0.00 C+0
ATOM 11 C 0 -1.492 1.445 0.042 0.00 0.00 C+0
ATOM 12 C 0 -2.582 0.629 -0.006 0.00 0.00 C+0
ATOM 13 C 0 -3.795 1.453 0.021 0.00 0.00 C+0
ATOM 14 O 0 -4.931 1.020 -0.009 0.00 0.00 O+0
ATOM 15 O 0 -3.469 2.756 0.086 0.00 0.00 O+0
ATOM 16 C 0 -2.018 2.860 0.110 0.00 0.00 C+0
ATOM 17 C 0 -2.547 -0.850 -0.076 0.00 0.00 C+0
ATOM 18 C 0 -3.142 -1.612 0.928 0.00 0.00 C+0
ATOM 19 C 0 -3.107 -2.990 0.857 0.00 0.00 C+0
ATOM 20 C 0 -2.482 -3.615 -0.207 0.00 0.00 C+0
ATOM 21 C 0 -1.889 -2.864 -1.206 0.00 0.00 C+0
ATOM 22 C 0 -1.923 -1.485 -1.150 0.00 0.00 C+0
ATOM 23 H 0 6.153 0.853 1.027 0.00 0.00 H+0
ATOM 24 H 0 4.930 2.022 0.474 0.00 0.00 H+0
ATOM 25 H 0 4.665 1.097 1.972 0.00 0.00 H+0
ATOM 26 H 0 2.754 1.399 -1.772 0.00 0.00 H+0
ATOM 27 H 0 0.398 2.100 -1.773 0.00 0.00 H+0
ATOM 28 H 0 -0.241 -0.133 1.841 0.00 0.00 H+0
ATOM 29 H 0 2.118 -0.823 1.815 0.00 0.00 H+0
ATOM 30 H 0 -1.693 3.344 1.032 0.00 0.00 H+0
ATOM 31 H 0 -1.668 3.426 -0.753 0.00 0.00 H+0
ATOM 32 H 0 -3.630 -1.126 1.760 0.00 0.00 H+0
ATOM 33 H 0 -3.568 -3.582 1.634 0.00 0.00 H+0
ATOM 34 H 0 -2.456 -4.693 -0.258 0.00 0.00 H+0
ATOM 35 H 0 -1.402 -3.357 -2.035 0.00 0.00 H+0
ATOM 36 H 0 -1.460 -0.900 -1.931 0.00 0.00 H+0
CONECT 1 2 23 24 25 NONE 41
CONECT 2 1 3 4 5 NONE 42
CONECT 3 2 0 0 0 NONE 43
CONECT 4 2 0 0 0 NONE 44
CONECT 5 2 10 6 0 NONE 45
CONECT 6 5 7 26 0 NONE 46
CONECT 7 6 8 27 0 NONE 47
CONECT 8 7 9 11 0 NONE 48
CONECT 9 8 10 28 0 NONE 49
CONECT 10 9 5 29 0 NONE 50
CONECT 11 8 16 12 0 NONE 51
CONECT 12 11 13 17 0 NONE 52
CONECT 13 12 14 15 0 NONE 53
CONECT 14 13 0 0 0 NONE 54
CONECT 15 13 16 0 0 NONE 55
CONECT 16 15 11 30 31 NONE 56
CONECT 17 12 22 18 0 NONE 57
CONECT 18 17 19 32 0 NONE 58
CONECT 19 18 20 33 0 NONE 59
CONECT 20 19 21 34 0 NONE 60
CONECT 21 20 22 35 0 NONE 61
CONECT 22 21 17 36 0 NONE 62
END NONE 63 NONE 63</inlineContents>
</jmolApplet>
</jmol>
|-
|}
'''Vioxx''', also known as Rofecoxib, is a nonsteroidal anti-inflammatory drug (NSAID) with the IUPAC systematic name of 4-(4-methylsulfonylphenyl)-3-phenyl-5H-furan-2-one. It was developed by Merck & Co. to relieve the pain, tenderness, inflammation and stiffness caused by arthritis and to treat painful menstrual periods. Rofecoxib is a selective and orally active inhibitor of Cyclooxygenase-2.

Merck & Co. have announced the voluntary worldwide withdrawal of rofecoxib on 30th September 2004 after concerns of an increased risk of cardiovascular events such as heart attack and stroke was discovered in patients taking rofecoxib.[http://www.vioxx.com/rofecoxib/vioxx/consumer/index.jsp 1]

==Synthesis of rofecoxib==

'''1'''. ''Rofecoxib''

'''2'''. ''Thioanisole''

'''3'''. ''Acetophenone'' - prepared by the Friedel-Crafts acylation of thioanysole ('''2''')

'''4'''. ''Sulfone'' - prepared by the oxidation of acetophenone ('''3''') with MMPP, magnesium monoperoxyphthalate hexahydrate

'''5'''. ''Bromoketone'' - prepared by the reaction of the sulfone ('''4''') with bromine in chloroform at -5°C in the presence of a trace amount of AlCl<sub>3</sub>

'''1'''. ''Rofecoxib'' - bromoketone ('''5''') coupled and cyclized in a two step, one pot procedure with phenylacetic acid

[[Image:vioxxsy.png]]

==Mechanism of action==

Rofecoxib belongs to a group of drugs called the nonsteroidal anti-inflammatory drugs (NSAID). They are drugs with analgesic (reduce pain), antipyretic (reduce fever) and anti-inflammatory (reduce inflammation) effects. Most NSAIDs act as non-selective inhibitors of the enzyme cyclooxygenase, inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. Rofecoxib is an NSAID that selectively acts only on the cyclooxygenase-2 (COX-2) isoenzyme. This selectivity was thought to be beneficial because COX-2 is responsible for pain and inflammation and COX-1 is responsible for the protection of the stomach lining. Therefore, the drug developers were aiming for an NSAID without the side effects to the gastrointestinal system.[http://www.medinfo.co.uk/drugs/nsaids.html 2]

==How does Vioxx works==

Rofecoxib works by inhibiting prostaglandin production, primarily by the inhibition of cyclooxygenase-2. It does not inhibit cyclooxygenase-1, which supposedly makes it easier on the stomach than traditional NSAIDs.[http://arthritisinsight.com/medical/meds/vioxx.html (A)]

==Side effects of Vioxx==

Allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives),

Abdominal pain,

Tenderness,

Discomfort;

Nausea;

Blood in your vomit;

Bloody,

Black,

Tarry stools;

Unexplained weight gain;

Swelling or water retention;

Fatigue or lethargy; a skin rash;

Itching;

Yellowing of your skin or eyes;

"Flu-like" symptoms;

Unusual bruising or bleeding.

==Legal status==

Rofecoxib was initially FDA-approved on 21st May 1999.

== 3D Structure ==

<jmol>
<jmolApplet>
<size>300</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 -4.931 1.018 -0.011 0.00 0.00 O+0
ATOM 2 C 0 -3.796 1.451 0.018 0.00 0.00 C+0
ATOM 3 O 0 -3.469 2.755 0.080 0.00 0.00 O+0
ATOM 4 C 0 -2.019 2.859 0.098 0.00 0.00 C+0
ATOM 5 C 0 -1.493 1.444 0.038 0.00 0.00 C+0
ATOM 6 C 0 -0.084 1.030 0.032 0.00 0.00 C+0
ATOM 7 C 0 0.746 1.371 -1.043 0.00 0.00 C+0
ATOM 8 C 0 2.067 0.979 -1.041 0.00 0.00 C+0
ATOM 9 C 0 2.574 0.249 0.020 0.00 0.00 C+0
ATOM 10 S 0 4.265 -0.247 0.013 0.00 0.00 S+0
ATOM 11 C 0 5.105 1.137 0.831 0.00 0.00 C+0
ATOM 12 O 0 4.255 -1.410 0.830 0.00 0.00 O+0
ATOM 13 O 0 4.572 -0.300 -1.373 0.00 0.00 O+0
ATOM 14 C 0 1.761 -0.093 1.087 0.00 0.00 C+0
ATOM 15 C 0 0.439 0.297 1.103 0.00 0.00 C+0
ATOM 16 C 0 -2.582 0.628 -0.003 0.00 0.00 C+0
ATOM 17 C 0 -2.547 -0.852 -0.067 0.00 0.00 C+0
ATOM 18 C 0 -3.045 -1.610 0.993 0.00 0.00 C+0
ATOM 19 C 0 -3.010 -2.988 0.927 0.00 0.00 C+0
ATOM 20 C 0 -2.482 -3.617 -0.186 0.00 0.00 C+0
ATOM 21 C 0 -1.987 -2.870 -1.240 0.00 0.00 C+0
ATOM 22 C 0 -2.021 -1.492 -1.189 0.00 0.00 C+0
ATOM 23 H 0 -1.674 3.424 -0.768 0.00 0.00 H+0
ATOM 24 H 0 -1.689 3.343 1.017 0.00 0.00 H+0
ATOM 25 H 0 0.351 1.940 -1.872 0.00 0.00 H+0
ATOM 26 H 0 2.708 1.241 -1.869 0.00 0.00 H+0
ATOM 27 H 0 4.710 1.257 1.840 0.00 0.00 H+0
ATOM 28 H 0 6.175 0.933 0.883 0.00 0.00 H+0
ATOM 29 H 0 4.936 2.051 0.263 0.00 0.00 H+0
ATOM 30 H 0 2.165 -0.663 1.911 0.00 0.00 H+0
ATOM 31 H 0 -0.194 0.030 1.937 0.00 0.00 H+0
ATOM 32 H 0 -3.457 -1.121 1.863 0.00 0.00 H+0
ATOM 33 H 0 -3.394 -3.577 1.747 0.00 0.00 H+0
ATOM 34 H 0 -2.456 -4.696 -0.233 0.00 0.00 H+0
ATOM 35 H 0 -1.576 -3.367 -2.107 0.00 0.00 H+0
ATOM 36 H 0 -1.634 -0.910 -2.012 0.00 0.00 H+0
CONECT 1 2 0 0 0 NONE 41
CONECT 2 1 16 3 0 NONE 42
CONECT 3 2 4 0 0 NONE 43
CONECT 4 3 5 23 24 NONE 44
CONECT 5 4 6 16 0 NONE 45
CONECT 6 5 15 7 0 NONE 46
CONECT 7 6 8 25 0 NONE 47
CONECT 8 7 9 26 0 NONE 48
CONECT 9 8 10 14 0 NONE 49
CONECT 10 9 11 12 13 NONE 50
CONECT 11 10 27 28 29 NONE 51
CONECT 12 10 0 0 0 NONE 52
CONECT 13 10 0 0 0 NONE 53
CONECT 14 9 15 30 0 NONE 54
CONECT 15 14 6 31 0 NONE 55
CONECT 16 5 2 17 0 NONE 56
CONECT 17 16 22 18 0 NONE 57
CONECT 18 17 19 32 0 NONE 58
CONECT 19 18 20 33 0 NONE 59
CONECT 20 19 21 34 0 NONE 60
CONECT 21 20 22 35 0 NONE 61
CONECT 22 21 17 36 0 NONE 62
END NONE 63</inlineContents>
</jmolApplet>
</jmol>

==References==

File:Vioxx2.png

2006-11-24T15:40:42Z

Gld04:

2006-11-24T14:04:22Z

Gld04: /* References */

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}}| '''Vioxx (treatment of osteoarthritis symptoms and pain)'''

|-
| align="center" colspan="2" bgcolor="#ffffff" |[[Image:Vioxx1.png]]
|-
| [[IUPAC nomenclature|Chemical name]]
| ''12(5H)-Furanone,

4-[4-(methylsulfonyl)phenyl]-3-phenyl- (9CI)''
|-
| [[CAS nummber]]
| 162011-90-7
|-
| [[Chemical formula]]
| C17 H14 O4 S
|-
| [[Molecular mass]]
| {{{mol_mass|314.355768 g/mol
|-
| Melting point
| 204.7°C [http://lfp.mimas.ac.uk/lfp/LinkFinderPlus/Display?&PAG=1778+-+1779&CNR=6311904&AU=Therien,+Michel%3b+Gauthier,+Jacques+Yves%3b+Leblanc,+Yves%3b+Leger,+Serge%3b+Perrier,+Helene%3b+Prasit,+Petpiboon%3b+Wang,+Zhaoyin&NB=12&LA=EN&PY=2001&JT=Synthesis&CO=SYNTBF&CED=2002%2f03%2f31&DT=Journal&_Origin=Beilstein]
|-
| [[H2O Solubility]]
| Insoluble
|-
| [[State]]
| Solid
|-
| [[Drug Category]]
| Anti-Inflammatory Agents,

Non-Steroidal

Cyclooxygenase Inhibitors
|-
| [[Indication]]
| For the treatment of osteoarthritis,

acute pain in adults and menstrual pain.
|-
| [[Toxicity]]
| No overdoses of rofecoxib were reported

during clinical trials. Administration of

single doses of rofecoxib 1000 mg to 6 healthy

volunteers and multiple doses of 250 mg/day

for 14 days to 75 healthy volunteers did not

result in serious toxicity.
|-
| [[Protein Binding]]
| 87%
|-
| [[Half Life]]
| 17 Hours
|-
| And here is a 3D picture:[http://redpoll.pharmacy.ualberta.ca/drugbank/drugBank/drugPDB_unzipped/APRD00151_PDB.txt (1)]
|
<jmol>
<jmolApplet>
<size>325</size>
<color>white</color>
<script>zoom 125; cpk off;frame 1; move 100 -100 100 0 0 0 0 0 2; delay 1;</script>
<inlineContents>water.mol
title1
title2

ATOM 1 C 0 5.085 1.062 0.967 0.00 0.00 C+0
ATOM 2 S 0 4.266 -0.246 0.015 0.00 0.00 S+0
ATOM 3 O 0 4.606 -0.182 -1.363 0.00 0.00 O+0
ATOM 4 O 0 4.236 -1.474 0.729 0.00 0.00 O+0
ATOM 5 C 0 2.575 0.250 0.023 0.00 0.00 C+0
ATOM 6 C 0 2.093 1.068 -0.985 0.00 0.00 C+0
ATOM 7 C 0 0.772 1.461 -0.986 0.00 0.00 C+0
ATOM 8 C 0 -0.083 1.031 0.035 0.00 0.00 C+0
ATOM 9 C 0 0.412 0.204 1.050 0.00 0.00 C+0
ATOM 10 C 0 1.735 -0.184 1.033 0.00 0.00 C+0
ATOM 11 C 0 -1.492 1.445 0.042 0.00 0.00 C+0
ATOM 12 C 0 -2.582 0.629 -0.006 0.00 0.00 C+0
ATOM 13 C 0 -3.795 1.453 0.021 0.00 0.00 C+0
ATOM 14 O 0 -4.931 1.020 -0.009 0.00 0.00 O+0
ATOM 15 O 0 -3.469 2.756 0.086 0.00 0.00 O+0
ATOM 16 C 0 -2.018 2.860 0.110 0.00 0.00 C+0
ATOM 17 C 0 -2.547 -0.850 -0.076 0.00 0.00 C+0
ATOM 18 C 0 -3.142 -1.612 0.928 0.00 0.00 C+0
ATOM 19 C 0 -3.107 -2.990 0.857 0.00 0.00 C+0
ATOM 20 C 0 -2.482 -3.615 -0.207 0.00 0.00 C+0
ATOM 21 C 0 -1.889 -2.864 -1.206 0.00 0.00 C+0
ATOM 22 C 0 -1.923 -1.485 -1.150 0.00 0.00 C+0
ATOM 23 H 0 6.153 0.853 1.027 0.00 0.00 H+0
ATOM 24 H 0 4.930 2.022 0.474 0.00 0.00 H+0
ATOM 25 H 0 4.665 1.097 1.972 0.00 0.00 H+0
ATOM 26 H 0 2.754 1.399 -1.772 0.00 0.00 H+0
ATOM 27 H 0 0.398 2.100 -1.773 0.00 0.00 H+0
ATOM 28 H 0 -0.241 -0.133 1.841 0.00 0.00 H+0
ATOM 29 H 0 2.118 -0.823 1.815 0.00 0.00 H+0
ATOM 30 H 0 -1.693 3.344 1.032 0.00 0.00 H+0
ATOM 31 H 0 -1.668 3.426 -0.753 0.00 0.00 H+0
ATOM 32 H 0 -3.630 -1.126 1.760 0.00 0.00 H+0
ATOM 33 H 0 -3.568 -3.582 1.634 0.00 0.00 H+0
ATOM 34 H 0 -2.456 -4.693 -0.258 0.00 0.00 H+0
ATOM 35 H 0 -1.402 -3.357 -2.035 0.00 0.00 H+0
ATOM 36 H 0 -1.460 -0.900 -1.931 0.00 0.00 H+0
CONECT 1 2 23 24 25 NONE 41
CONECT 2 1 3 4 5 NONE 42
CONECT 3 2 0 0 0 NONE 43
CONECT 4 2 0 0 0 NONE 44
CONECT 5 2 10 6 0 NONE 45
CONECT 6 5 7 26 0 NONE 46
CONECT 7 6 8 27 0 NONE 47
CONECT 8 7 9 11 0 NONE 48
CONECT 9 8 10 28 0 NONE 49
CONECT 10 9 5 29 0 NONE 50
CONECT 11 8 16 12 0 NONE 51
CONECT 12 11 13 17 0 NONE 52
CONECT 13 12 14 15 0 NONE 53
CONECT 14 13 0 0 0 NONE 54
CONECT 15 13 16 0 0 NONE 55
CONECT 16 15 11 30 31 NONE 56
CONECT 17 12 22 18 0 NONE 57
CONECT 18 17 19 32 0 NONE 58
CONECT 19 18 20 33 0 NONE 59
CONECT 20 19 21 34 0 NONE 60
CONECT 21 20 22 35 0 NONE 61
CONECT 22 21 17 36 0 NONE 62
END NONE 63 NONE 63</inlineContents>
</jmolApplet>
</jmol>
|-
|}
'''Vioxx''', also known as Rofecoxib, is a nonsteroidal anti-inflammatory drug (NSAID) with the IUPAC systematic name of 4-(4-methylsulfonylphenyl)-3-phenyl-5H-furan-2-one. It was developed by Merck & Co. to relieve the pain, tenderness, inflammation and stiffness caused by arthritis and to treat painful menstrual periods. Rofecoxib is a selective and orally active inhibitor of Cyclooxygenase-2.

Merck & Co. have announced the voluntary worldwide withdrawal of rofecoxib on 30th September 2004 after concerns of an increased risk of cardiovascular events such as heart attack and stroke was discovered in patients taking rofecoxib.[http://www.vioxx.com/rofecoxib/vioxx/consumer/index.jsp 1]

==Synthesis of rofecoxib==

'''1'''. ''Rofecoxib''

'''2'''. ''Thioanisole''

'''3'''. ''Acetophenone'' - prepared by the Friedel-Crafts acylation of thioanysole ('''2''')

'''4'''. ''Sulfone'' - prepared by the oxidation of acetophenone ('''3''') with MMPP, magnesium monoperoxyphthalate hexahydrate

'''5'''. ''Bromoketone'' - prepared by the reaction of the sulfone ('''4''') with bromine in chloroform at -5°C in the presence of a trace amount of AlCl<sub>3</sub>

'''1'''. ''Rofecoxib'' - bromoketone ('''5''') coupled and cyclized in a two step, one pot procedure with phenylacetic acid

[[Image:vioxxsy.png]]

==Mechanism of action==

Rofecoxib belongs to a group of drugs called the nonsteroidal anti-inflammatory drugs (NSAID). They are drugs with analgesic (reduce pain), antipyretic (reduce fever) and anti-inflammatory (reduce inflammation) effects. Most NSAIDs act as non-selective inhibitors of the enzyme cyclooxygenase, inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. Rofecoxib is an NSAID that selectively acts only on the cyclooxygenase-2 (COX-2) isoenzyme. This selectivity was thought to be beneficial because COX-2 is responsible for pain and inflammation and COX-1 is responsible for the protection of the stomach lining. Therefore, the drug developers were aiming for an NSAID without the side effects to the gastrointestinal system.[http://www.medinfo.co.uk/drugs/nsaids.html 2]

==Side effects of Vioxx==

Allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives),

Abdominal pain,

Tenderness,

Discomfort;

Nausea;

Blood in your vomit;

Bloody,

Black,

Tarry stools;

Unexplained weight gain;

Swelling or water retention;

Fatigue or lethargy; a skin rash;

Itching;

Yellowing of your skin or eyes;

"Flu-like" symptoms;

Unusual bruising or bleeding.

==Legal status==

Rofecoxib was initially FDA-approved on 21st May 1999.

== 3D Structure ==

<jmol>
<jmolApplet>
<size>300</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 -4.931 1.018 -0.011 0.00 0.00 O+0
ATOM 2 C 0 -3.796 1.451 0.018 0.00 0.00 C+0
ATOM 3 O 0 -3.469 2.755 0.080 0.00 0.00 O+0
ATOM 4 C 0 -2.019 2.859 0.098 0.00 0.00 C+0
ATOM 5 C 0 -1.493 1.444 0.038 0.00 0.00 C+0
ATOM 6 C 0 -0.084 1.030 0.032 0.00 0.00 C+0
ATOM 7 C 0 0.746 1.371 -1.043 0.00 0.00 C+0
ATOM 8 C 0 2.067 0.979 -1.041 0.00 0.00 C+0
ATOM 9 C 0 2.574 0.249 0.020 0.00 0.00 C+0
ATOM 10 S 0 4.265 -0.247 0.013 0.00 0.00 S+0
ATOM 11 C 0 5.105 1.137 0.831 0.00 0.00 C+0
ATOM 12 O 0 4.255 -1.410 0.830 0.00 0.00 O+0
ATOM 13 O 0 4.572 -0.300 -1.373 0.00 0.00 O+0
ATOM 14 C 0 1.761 -0.093 1.087 0.00 0.00 C+0
ATOM 15 C 0 0.439 0.297 1.103 0.00 0.00 C+0
ATOM 16 C 0 -2.582 0.628 -0.003 0.00 0.00 C+0
ATOM 17 C 0 -2.547 -0.852 -0.067 0.00 0.00 C+0
ATOM 18 C 0 -3.045 -1.610 0.993 0.00 0.00 C+0
ATOM 19 C 0 -3.010 -2.988 0.927 0.00 0.00 C+0
ATOM 20 C 0 -2.482 -3.617 -0.186 0.00 0.00 C+0
ATOM 21 C 0 -1.987 -2.870 -1.240 0.00 0.00 C+0
ATOM 22 C 0 -2.021 -1.492 -1.189 0.00 0.00 C+0
ATOM 23 H 0 -1.674 3.424 -0.768 0.00 0.00 H+0
ATOM 24 H 0 -1.689 3.343 1.017 0.00 0.00 H+0
ATOM 25 H 0 0.351 1.940 -1.872 0.00 0.00 H+0
ATOM 26 H 0 2.708 1.241 -1.869 0.00 0.00 H+0
ATOM 27 H 0 4.710 1.257 1.840 0.00 0.00 H+0
ATOM 28 H 0 6.175 0.933 0.883 0.00 0.00 H+0
ATOM 29 H 0 4.936 2.051 0.263 0.00 0.00 H+0
ATOM 30 H 0 2.165 -0.663 1.911 0.00 0.00 H+0
ATOM 31 H 0 -0.194 0.030 1.937 0.00 0.00 H+0
ATOM 32 H 0 -3.457 -1.121 1.863 0.00 0.00 H+0
ATOM 33 H 0 -3.394 -3.577 1.747 0.00 0.00 H+0
ATOM 34 H 0 -2.456 -4.696 -0.233 0.00 0.00 H+0
ATOM 35 H 0 -1.576 -3.367 -2.107 0.00 0.00 H+0
ATOM 36 H 0 -1.634 -0.910 -2.012 0.00 0.00 H+0
CONECT 1 2 0 0 0 NONE 41
CONECT 2 1 16 3 0 NONE 42
CONECT 3 2 4 0 0 NONE 43
CONECT 4 3 5 23 24 NONE 44
CONECT 5 4 6 16 0 NONE 45
CONECT 6 5 15 7 0 NONE 46
CONECT 7 6 8 25 0 NONE 47
CONECT 8 7 9 26 0 NONE 48
CONECT 9 8 10 14 0 NONE 49
CONECT 10 9 11 12 13 NONE 50
CONECT 11 10 27 28 29 NONE 51
CONECT 12 10 0 0 0 NONE 52
CONECT 13 10 0 0 0 NONE 53
CONECT 14 9 15 30 0 NONE 54
CONECT 15 14 6 31 0 NONE 55
CONECT 16 5 2 17 0 NONE 56
CONECT 17 16 22 18 0 NONE 57
CONECT 18 17 19 32 0 NONE 58
CONECT 19 18 20 33 0 NONE 59
CONECT 20 19 21 34 0 NONE 60
CONECT 21 20 22 35 0 NONE 61
CONECT 22 21 17 36 0 NONE 62
END NONE 63</inlineContents>
</jmolApplet>
</jmol>

==References==