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

The in vivo anti-thrombotic activities of amino acid modified tetrahydro-β-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-β-carboline derivatives was performed and N-[(1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-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-β-carboline-3-carbonyl]-N′-(amino-acid-acyl)hydrazines were orally efficacious.

Eighteen novel N-[(1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carbonyl]-N′-(amino-acid-acyl)hydrazines were explored having stretching conformation and to be orally anti-thrombotic active at a dose of 10 nmol/kg for the first time.Figure optionsDownload as PowerPoint slideHighlights
► Conformation was used to predict the anti-thrombotic activity of amino acid modified β-carbolines.
► A stretching conformation is essential for amino acid modified β-carboline to have high anti-thrombotic activity.
► Due to stretching conformation the effective dose of amino acid modified β-carbonylhydrazines was 10 nmol/kg only.