1,3-Diarylcycloalkanopyrazoles and diphenyl hydrazides as selective inhibitors of cyclooxygenase-2.
Novel 1,3-diarylcycloalkanopyrazoles 1, and diphenyl hydrazides 2 were identified as selective inhibitors of cyclooxygenase-2. The 1,3-diaryl substitution pattern of the pyrazole ring in 1 differentiates these compounds from most of the known selective COX-2 inhibitors that contain two aryl rings at the adjacent positions on a heterocyclic or a phenyl ring. Similarly, the two phenyl rings in 2 are also separated by three atoms. SAR of both phenyl rings in 1 and 2, and the aliphatic ring in 1 will be discussed.
Sui
Z
Z
The R.W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869, USA.
Guan
J
J
Ferro
M P
MP
McCoy
K
K
Wachter
M P
MP
Murray
W V
WV
Singer
M
M
Steber
M
M
Ritchie
D M
DM
Argentieri
D C
DC
D001386:Azides / Q000138:chemical synthesis* / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001386:Azides; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases