566151-57-3Relevant academic research and scientific papers
Synthesis of 2-azabicyclo[4.1.0]heptanes through stereoselective cyclopropanation reactions
Suarez Del Villar, Irene,Gradillas, Ana,Perez-Castells, Javier
experimental part, p. 5850 - 5862 (2011/03/17)
Unsaturated δ-lactams are cyclopropanated with the aid of diazo compound decomposition catalysed by metal complexes. A study of the reaction conditions, stereochemical outcome and group protection is reported. The resulting bicyclic products are related to bioactive compounds. Transformation into thiolactams facilitates the separation of the different isomers obtained and the removal of the protecting group. The cyclopropanation reaction works with diverse diazo compounds. Unsaturated δ-lactams are cyclopropanated with the aid of diazo compound decomposition catalysed by metal complexes. A study of the reaction conditions, stereochemical outcome and group protection isreported. Transformation into thiolactams assists in separation of the different isomers obtained and removal of the protecting group.
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.
