Inhibition of inducible nitric oxide synthase by acetamidine derivatives of hetero-substituted lysine and homolysine

…, DM Coe, CL Chambers, PI Davies, J Dawson…

Index: Young, Robert J.; Beams, Richard M.; Carter, Keith; Clark, Helen A.R.; Coe, Diane M.; Chambers, C. Lynn; Davies, P. Ifeyinwa; Dawson, John; Drysdale, Martin J.; Franzman, Karl W.; French, Colin; Hodgson, Simon T.; Hodson, Harold F.; Kleanthous, Savvas; Rider, Peter; Sanders, Daniela; Sawyer, David A.; Scott, Keith J.; Shearer, Barry G.; Stocker, Richard; Smith, Steven; Tackley, Miriam C.; Knowles, Richard G. Bioorganic and Medicinal Chemistry Letters, 2000 , vol. 10, # 6 p. 597 - 600

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Citation Number: 83

Abstract

The acetamidine derivatives of l-ornithine (l-N-iminoethylornithine, l-NIO) 12 and l-lysine (l-NIL), 13 analogues of the NOS substrate l-arginine, are potent inhibitors of iNOS, with both compounds showing some selectivity over the constitutive isoforms. In this paper we report on the synthesis and SAR of hetero-substituted analogues and homologues of l-NIL, including the sulphone GW273629 and sulphide GW274150, which have similar potency to l-NIL and ...