Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases.
A series of 3- and 5-imino analogs from oxazepane, thiazepane, and diazepane was prepared and evaluated as inhibitors of human nitric oxide synthesis (NOS). The most potent iNOS inhibitor was the thiazepane analog 25 (IC(50) = 0.19 microM).
Shankaran
K
K
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. kothandaraman_shankaran@merck.com
Donnelly
Karla L
KL
Shah
Shrenik K
SK
Caldwell
Charles G
CG
Chen
Ping
P
Hagmann
William K
WK
Maccoss
Malcolm
M
Humes
John L
JL
Pacholok
Stephen G
SG
Kelly
Theresa M
TM
Grant
Stephan K
SK
Wong
Kenny K
KK
D001389:Azirines / Q000138:chemical synthesis / Q000494:pharmacology; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010077:Oxazepines / Q000138:chemical synthesis* / Q000494:pharmacology; D013841:Thiazepines / Q000138:chemical synthesis* / Q000494:pharmacology
D001389:Azirines; D004095:Dihydropyridines; D004791:Enzyme Inhibitors; D010077:Oxazepines; D013841:Thiazepines; C069267:diazipine; D019001:Nitric Oxide Synthase