Conformationally restricted arginine analogues as inhibitors of human nitric oxide synthase

Conformationally restricted analogues of the endogenous NOS substrate L-arginine and the arginine based NOS inhibitors N-G-methyl-L-arginine (L-NMA) and N-delta-iminoethyl-L-ornithine (L-NIO) were synthesized for evaluation as inhibitors of human NOS. Incorporation of a phenyl ring into the C4-C5 backbone chain provided 2-aminophenylalanine analogues which retained potent NOS inhibition. Structurally related analogues of 3-aminophenylalanine were significantly weaker inhibitors. (C) 1997 Elsevier Science Ltd.