Hah, JM Martasek, P Roman, LJ Silverman, RB 2024-01-21T09:03:49Z 2024-01-21T09:03:49Z 2021-09-01 2003-04-24 0022-2623 https://pubs.kist.re.kr/handle/201004/138638 Nitric oxide synthase inhibitors could act as important therapies for disorders arising from overstimulation or overexpression of individual nitric oxide synthase (NOS) isoforms. But preservation of physiologically important nitric oxide functions require the use of isoform-selective inhibitors. Recently we reported reduced amide bond pseudodipeptide analogues as potent and selective neuronal nitric oxide synthase (nNOS) inhibitors (Hah, J.-M.; Roman, L. J.; Martasek, P.; Silverman, R. B. J. Med. Chem. 2001, 44, 2667-2670). To increase the lipophilicity a series of aromatic, reduced amide bond analogues (6-25) were designed and synthesized as potential selective nNOS inhibitors. The hypothesized large increase in isoform selectivity of nNOS over inducible NOS was not obtained in this series. However, the high potency with nNOS as well as high selectivity of nNOS over endothelial NOS was retained in some of these compounds (15, 17, 21), as well as good selectivity over inducible NOS. The most potent nNOS inhibitor among these compounds is N-(4S)-{4-amino-5-[2-(2-aminoethyl)phenylamino]-pentyl}-N'-nitroguanidine (17) (K-i = 50 nM), which also shows the highest selectivity over eNOS (greater than 2100-fold) and 70-fold selectivity over iNOS. Further modification of compound 17 should lead to even more potent and selective nNOS inhibitors. English AMER CHEMICAL SOC CONTAINING DIPEPTIDE AMIDES ESCHERICHIA-COLI ARGININE RELEASE POTENT Aromatic reduced amide bond peptidomimetics as selective inhibitors of neuronal nitric oxide synthase Article 10.1021/jm0202932 1 JOURNAL OF MEDICINAL CHEMISTRY, v.46, no.9, pp.1661 - 1669 JOURNAL OF MEDICINAL CHEMISTRY 46 9 1661 1669 scie scopus 000182488300011 Chemistry, Medicinal Pharmacology & Pharmacy Article CONTAINING DIPEPTIDE AMIDES ESCHERICHIA-COLI ARGININE RELEASE POTENT