3,4-Diaryl-5-hydroxyfuranones: highly selective inhibitors of cyclooxygenase-2 with aqueous solubility.
The introduction of a hydroxyl group into the 5-position of the diaryl furanone system provides highly selective inhibitors of cyclooxygenase-2. These molecules can be converted into their sodium salts which are water soluble, facilitating intravenous formulation. These salts show excellent potency in rat models of pain, fever and inflammation.
Black
W Cameron
WC
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe-Claire-Dorval, Quebec, Canada H9R 4P8. blackc@merck.com
Brideau
Christine
C
Chan
Chi Chung
CC
Charleson
Stella
S
Cromlish
Wanda
W
Gordon
Robert
R
Grimm
Erich L
EL
Hughes
Gregory
G
Leger
Serge
S
Li
Chun Sing
CS
Riendeau
Denis
D
Thérien
Michel
M
Wang
Zhaoyin
Z
Xu
Li Jing
LJ
Prasit
Petpiboon
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy; D016466:CHO Cells; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006224:Cricetinae; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases