Preparation and evaluation of new l-canavanine derivatives as nitric oxide synthase inhibitors

New derivatives of the amino acid l-canavanine were prepared by total chemical synthesis and evaluated as inhibitors of inducible nitric oxide synthase (NOS). Replacement of the δ-methylene group of known NOS inhibitors with an oxygen atom produced dramatic effects as to the ability of these compounds to interact with the enzyme. These results indicate that the addition 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.