Discovery of novel leukotriene A4 hydrolase inhibitors based on piperidine and piperazine scaffolds.
Novel piperidine and piperazine derivatives have been designed and tested as inhibitors of LTA(4) hydrolase (LTA(4)H). Most potent compounds showed good potency in both enzymatic and functional human whole blood assay. Crystallography studies further confirmed observed structure-activity relationship and LTA(4)H binding mode for analogs from the piperidine series.
Sandanayaka
Vincent
V
Medicinal Chemistry Department, deCODE Chemistry, Inc. 2501 Davey Road, Woodridge, IL 60517, United States.
Mamat
Bjorn
B
Bhagat
Nikhil
N
Bedell
Louis
L
Halldorsdottir
Gudrun
G
Sigthorsdottir
Heida
H
Andrésson
Thorkell
T
Kiselyov
Alex
A
Gurney
Mark
M
Singh
Jasbir
J
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D010879:Piperazines; D010880:Piperidines; D000077489:Piperazine; C032727:piperidine; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase