Document Report Card

Basic Information

ID: ALA1136028

Journal: Bioorg Med Chem Lett

Title: Design and synthesis of orally bioavailable inhibitors of inducible nitric oxide synthase. Part 1: synthesis and biological evaluation of dihydropyridin-2-imines.

Authors: Kawanaka Y, Kobayashi K, Kusuda S, Tatsumi T, Murota M, Nishiyama T, Hisaichi K, Fujii A, Hirai K, Naka M, Komeno M, Nakai H, Toda M.

Abstract: Dihydropyridin-2-imines were synthesized and biologically evaluated both in vitro and in vivo using a nitric oxide inhibition assay. Compounds 1, 4, 5 and 7-11 exhibited potent activity in the inducible nitric oxide (iNOS) inhibition assay. Of these 5, 6, 9 and 10 showed 5- to 11-fold increases in isoform selectivity. Compounds 1, 5, 9 and 10 showed potent inhibitory activity in the NOx accumulation assay in mice. Compounds 1 and 5 also showed good bioavailability (BA) when given orally.

CiteXplore: 12161118

DOI: 10.1016/s0960-894x(02)00455-9