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

Y Kawanaka, K Kobayashi, S Kusuda, T Tatsumi…

Index: Kawanaka, Yasufumi; Kobayashi, Kaoru; Kusuda, Shinya; Tatsumi, Tadashi; Murota, Masanori; Nishiyama, Toshihiko; Hisaichi, Katsuya; Fujii, Atsuko; Hirai, Keisuke; Naka, Masao; Komeno, Masaharu; Nakai, Hisao; Toda, Masaaki Bioorganic and Medicinal Chemistry Letters, 2002 , vol. 12, # 17 p. 2291 - 2294

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Citation Number: 14

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 ...