Design, synthesis, and activity of 2-imidazol-1-ylpyrimidine derived inducible nitric oxide synthase dimerization inhibitors

…, M Adler, D Arnaiz, K Eagen, S Erickson…

Index: Davey, David D.; Adler, Marc; Arnaiz, Damian; Eagen, Keith; Erickson, Shawn; Guilford, William; Kenrick, Margaret; Morrissey, Michael M.; Ohlmeyer, Mike; Pan, Gonghua; Paradkar, Vidyadhar M.; Parkinson, John; Polokoff, Mark; Saionz, Kurt; Santos, Cecile; Subramanyam, Babu; Vergona, Ron; Wei, Robert G.; Whitlow, Marc; Ye, Bin; Zhao, Zuchun; Devlin, James J.; Phillips, Gary Journal of Medicinal Chemistry, 2007 , vol. 50, # 6 p. 1146 - 1157

Full Text: HTML

Citation Number: 53

Abstract

By the screening of a combinatorial library for inhibitors of nitric oxide (NO) formation by the inducible isoform of nitric oxide synthase (iNOS) using a whole-cell assay, 2-(imidazol-1-yl) pyrimidines were identified. Compounds were found to inhibit the dimerization of iNOS monomers, thus preventing the formation of the dimeric, active form of the enzyme. Optimization led to the selection of the potent, selective, and orally available iNOS ...