Preparation and evaluation of new L-canavanine derivatives as nitric oxidesynthase inhibitors

New derivatives of the amino acid L-canavanine were prepared by total chemi cal synthesis and evaluated as inhibitors of inducible nitric oxide synthas e (NOS). Replacement of the delta -methylene group of known NOS inhibitors with an oxygen atom produced dramatic effects as to the ability of these co mpounds to interact with the enzyme. These results indicate that the additi on of an electron withdrawing group in the side chain of L-arginine-derived NOS inhibitors must be considered during inhibitor design depending on the expected mode of interaction with the enzyme. (C) 2001 Elsevier Science Lt d. All rights reserved.