Syntheses of new conformationally constrained S-[2-[(1-iminoethyl)amino] ethyl]homocysteine derivatives as potential nitric oxide synthase inhibitors

The efficient syntheses of two new types of conformationally constrained S-[2-[(1-iminoethyl)amino]ethyl]homocysteine derivatives, 1-amino-3-[2[(1-iminoethyl)amino]ethylthio]cyclobutane carboxylic Acid (5) and (4S)-4-[[2-[(1-Iminoethyl)amino]ethyl]thio]-L-proline (6), are reported. These molecules represent the first attempts to probe conformational constraint near the α-amino acid moiety of known homocysteine-based inhibitors of nitric oxide synthase. Targets 5 and 6 were evaluated as potential inhibitors of the three human isoforms of nitric oxide synthase. © 2002 John Wiley & Sons, Inc. Heteroatom Chem 13:77–83, 2002; DOI 10.1002/hc.1109