Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase

K Shankaran; Karla L Donnelly; Shrenik K Shah; Ravindra N Guthikonda; Malcolm MacCoss; John L Humes; Stephen G Pacholok; Stephan K Grant; T M Kelly; K K Wong

doi:10.1016/j.bmcl.2004.06.033

Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase

Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44. doi: 10.1016/j.bmcl.2004.06.033.

Authors

K Shankaran¹, Karla L Donnelly, Shrenik K Shah, Ravindra N Guthikonda, Malcolm MacCoss, John L Humes, Stephen G Pacholok, Stephan K Grant, T M Kelly, K K Wong

Affiliation

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

PMID: 15357988
DOI: 10.1016/j.bmcl.2004.06.033

Abstract

Syntheses and evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase (NOS) are discussed. An extensive SAR was established for pyrrolidin-2-imines class of compounds. The amidines came out as the most potent inhibitors in addition to displaying selectivity.

MeSH terms

Drug Evaluation, Preclinical / methods
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Imines / chemistry*
Imines / pharmacology
Nitric Oxide Synthase / antagonists & inhibitors*
Nitric Oxide Synthase / metabolism
Pyrrolidines / chemistry*
Pyrrolidines / pharmacology
Thiazoles / chemistry*
Thiazoles / pharmacology

Substances

Enzyme Inhibitors
Imines
Pyrrolidines
Thiazoles
Nitric Oxide Synthase