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

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 17; pp. 4539 - 4544
• Main Authors: Shankaran, K, Donnelly, Karla L, Shah, Shrenik K, Guthikonda, Ravindra N, MacCoss, Malcolm, Humes, John L, Pacholok, Stephen G, Grant, Stephan K, Kelly, T.M, Wong, K.K
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 06.09.2004; Elsevier
• Subjects: 1,3-Thiazolidin-2-imine; Biological and medical sciences; Drug Evaluation, Preclinical - methods; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Imines - chemistry; Imines - pharmacology; Medical sciences; Miscellaneous; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; NOS; Pharmacology. Drug treatments; Pyrrolidin-2-imine; Pyrrolidines - chemistry; Pyrrolidines - pharmacology; Thiazoles - chemistry; Thiazoles - pharmacology; Pyrrolidin-2-imine; 1,3-Thiazolidin-2-imine; NOS; Amidine; Enzyme; Enzyme inhibitor; Selectivity; Oxidoreductases; Chemical synthesis; Biological activity; Nitric-oxide synthase; Pyrrolidine derivatives
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.06.033

Synthesis and evaluation of pyrrolidin-2-imines (X = CHR 1) and 1,3-thiazolidin-2-imines (X = S) as inhibitors of nitric oxide synthase (NOS) are discussed. 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.