Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases

K Shankaran; Karla L Donnelly; Shrenik K Shah; Charles G Caldwell; Ping Chen; William K Hagmann; Malcolm Maccoss; John L Humes; Stephen G Pacholok; Theresa M Kelly; Stephan K Grant; Kenny K Wong

doi:10.1016/j.bmcl.2004.09.019

Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases

Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11. doi: 10.1016/j.bmcl.2004.09.019.

Authors

K Shankaran¹, Karla L Donnelly, Shrenik K Shah, Charles G Caldwell, Ping Chen, William K Hagmann, Malcolm Maccoss, John L Humes, Stephen G Pacholok, Theresa M Kelly, Stephan K Grant, Kenny K Wong

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. kothandaraman_shankaran@merck.com

PMID: 15501067
DOI: 10.1016/j.bmcl.2004.09.019

Abstract

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).

MeSH terms

Azirines / chemical synthesis
Azirines / pharmacology
Dihydropyridines / chemical synthesis
Dihydropyridines / pharmacology
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Humans
Nitric Oxide Synthase / antagonists & inhibitors*
Nitric Oxide Synthase / metabolism
Oxazepines / chemical synthesis*
Oxazepines / pharmacology
Thiazepines / chemical synthesis*
Thiazepines / pharmacology

Substances

Azirines
Dihydropyridines
Enzyme Inhibitors
Oxazepines
Thiazepines
diazipine
Nitric Oxide Synthase