1-(1,3-Benzodioxol-5-ylmethyl)-3-[4-(1H-imidazol-1-yl)phenoxy]-piperidine analogs as potent and selective inhibitors of nitric oxide formation.
A new series of 1-(1,3-benzodioxol-5-ylmethyl)-3-[4-(1H-Imidazol-1-yl)phenoxy]-piperidine analogs were designed and identified as potent and selective inhibitors of NO formation based both on the crystal structure of a murine iNOS Delta114 monomer domain/ inhibitor complex and inhibition of the NO formation in human A172 cell assays. Compound 12S showed high potency and high iNOS selectivity versus nNOS and eNOS.
Wei
Robert G
RG
Department of Medicinal Chemistry, Berlex Biosciences, 2600 Hilltop Drive, Richmond, CA 94804, USA. guo_ping_wei_@berlex.com
Adler
Marc
M
Davey
David
D
Ho
Elena
E
Mohan
Raju
R
Polokoff
Mark
M
Tseng
Jih-Lie
JL
Whitlow
Marc
M
Xu
Wei
W
Yuan
Shendong
S
Phillips
Gary
G
D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D008968:Molecular Conformation; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
C520997:1-(1,3-benzodioxol-5-ylmethyl)-3-(4-(1H-imidazol-1-yl)phenoxy)-piperidine; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010880:Piperidines; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III