Discovery of selective imidazole-based inhibitors of mammalian 15-lipoxygenase: highly potent against human enzyme within a cellular environment.
A series of 2,4,5-tri-substituted imidazoles has proven to be highly potent in inhibiting mammalian 15-lipoxygenase (15-LO) with excellent selectivity over human isozymes 5- and P-12-LO. Non-symmetrical sulfamides (e.g., 21a-n) were found to be suitable replacements for the earlier arylsulfonamide-containing members of this series (e.g., 2, 14a-p). Several members of these series also demonstrated potent inhibition of human 15-LO in a cell-based assay.
Weinstein
David S
DS
Department of Discovery Chemistry, Bristol-Myers Squibb, Research and Development, PO Box 4000, Princeton, NJ 08543-5400, USA. david.weinstein@bms.com
Liu
Wen
W
Ngu
Khehyong
K
Langevine
Charles
C
Combs
Donald W
DW
Zhuang
Shaobin
S
Chen
Cindy
C
Madsen
Cort S
CS
Harper
Timothy W
TW
Robl
Jeffrey A
JA
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D007093:Imidazoles; D016859:Lipoxygenase Inhibitors