Design and synthesis of orally bioavailable inhibitors of inducible nitric oxide synthase. Identification of 2-azabicyclo[4.1.0]heptan-3-imines
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.
PROCESS FOR THE PREPARATION OF INTERMEDIATE COMPOUNDS OF DRUGS
The present invention relates to a process for preparing selectively compound (I), (1S, 5S, 6R, 7R)-2-aza-7-chloro-5-methyl-3-oxobicyclo[4.1.0]heptane, by preparing compound (II) from compound (V) through compound (III) via a series of reactions, and by c
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(2010/01/31)
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