Heteroalicyclic carboxamidines as inhibitors of inducible nitric oxide synthase; the identification of (2R)-2-pyrrolidinecarboxamidine as a potent and selective haem-co …

…, D Brown, CL Chambers, MC Crowe, J Dawson…

Index: Young, Robert J.; Alderton, Wendy; Angell, Anthony D.R.; Beswick, Paul J.; Brown, David; Chambers, C. Lynn; Crowe, Miriam C.; Dawson, John; Hamlett, Christopher C.F.; Hodgson, Simon T.; Kleanthous, Savvas; Knowles, Richard G.; Russell, Linda J.; Stocker, Richard; Woolven, James M. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 10 p. 3037 - 3040

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Abstract

Abstract Heteroalicyclic carboxamidines were synthesised and evaluated as inhibitors of nitric oxide synthases.(2R)-2-Pyrrolidinecarboxamidine, in particular, was shown to be a highly potent in vitro (IC 50= 0.12 μM) and selective iNOS inhibitor (> 100-fold vs both eNOS and nNOS), with probable binding to the key anchoring glutamate residue and co-ordination to the haem iron.