566151-61-9Relevant academic research and scientific papers
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.
Design and synthesis of inhibitors of inducible nitric oxide synthase. Discovery of a new chemical lead with potential for oral bioavailability
Kawanaka, Yasufumi,Kobayashi, Kaoru,Kusuda, Shinya,Tatsumi, Tadashi,Murota, Masayuki,Nishiyama, Toshihiko,Hisaichi, Katsuya,Fujii, Atsuko,Hirai, Keisuke,Naka, Masao,Komeno, Masaharu,Nakai, Hisao,Toda, Masaaki
, p. 277 - 288 (2007/10/03)
A series of 2-iminopiperidines fused to small-membered rings (Tables 1 and 2) were synthesised and biologically evaluated using an in vitro human nitric oxide synthase (NOS) inhibition assay. Fused bicyclic compounds 5-9 exhibited nearly the same potency as compound 1 in the hiNOS inhibition assay. Among these, the 1-methyl analogues 8 and 9 showed better isoform selectivity than their corresponding unsubstituted analogues 7 and 6, respectively. Compounds 5 and 6 were also evaluated by an in vivo NO accumulation assay in a mouse model. The discovery process of new chemical leads for an orally bioavailable inhibitor of human inducible NOS (iNOS) is reported. The structure-activity relationship (SAR) study and chemistry of these compounds are also reported.
