A class of oral N-[(1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carbonyl]- N′-(amino-acid-acyl)hydrazine: Discovery, synthesis, in vitro anti-platelet aggregation/in vivo anti-thrombotic evaluation and 3D QSAR analysis

Abstract

The in vivo anti-thrombotic activities of amino acid modified tetrahydro-beta-carbolines depended upon the proximity of the side chain of the amino acid residue to the carboline-cycle. Based on this proximity the computerized screening of various tetrahydro-beta-carboline derivatives was performed and N-[(1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carbonyl]-N'-(amino-acid-acyl)hydrazines were explored having large proximity. The in vivo anti-thrombotic assays explored that at a dose of 10 nmol/kg eighteen novel N-[(1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carbonyl [-N'-(amino-acid-acyl)hydrazines were orally efficacious. (C) 2011 Elsevier Masson SAS. All rights reserved.