586398-55-2Relevant articles and documents
Design and synthesis of orally bioavailable inhibitors of inducible nitric oxide synthase. Identification of 2-azabicyclo[4.1.0]heptan-3-imines
Kawanaka, Yasufumi,Kobayashi, Kaoru,Kusuda, Shinya,Tatsumi, Tadashi,Murota, Masayuki,Nishiyama, Toshihiko,Hisaichi, Katsuya,Fujii, Atsuko,Hirai, Keisuke,Naka, Masao,Komeno, Masaharu,Odagaki, Yshihiko,Nakai, Hisao,Toda, Masaaki
, p. 1723 - 1743 (2007/10/03)
Further chemical modification of 2-iminopiperidines fused to cyclopropane rings was performed. Optically active isomers 2 and 13 were synthesized and their biological activity was evaluated. Compound 2 exhibited greater potency and more isoform selectivity than enantiomer 13 in the iNOS inhibition assay. One of the gem-chlorines on the fused cyclopropane moiety of 2 was eliminated to produce 3, which showed reduced potency for iNOS inhibition, as well as 4 with an increased potency. The isoform selectivity of 4 was also much higher than that of 3. This was also true for the corresponding methyl derivatives 6-9. The structure-activity relationship (SAR) study and computer aided docking study of the most optimized structure 4 with human iNOS will also be reported.
