CONFORMATIONALLY RESTRICTED ARGININE ANALOGS 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 f or evaluation as inhibitors of human NOS. Incorporation of a phenyl ri ng into the C4-C5 backbone chain provided 2-aminophenylalanine analogu es which retained potent NOS inhibition. Structurally related analogue s of 3-aminophenylalanine were significantly weaker inhibitors. (C) 19 97 Elsevier Science Ltd.