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.

Kun Yao, Ming Zhao, Xiaoyi Zhang, Yuji Wang, Li Li, Meiqing Zheng, Shiqi Peng, Kun Yao, Ming Zhao, Xiaoyi Zhang, Yuji Wang, Li Li, Meiqing Zheng, Shiqi Peng

Index: Eur. J. Med. Chem. 46 , 3237-49, (2011)

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Abstract

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.Copyright © 2011 Elsevier Ltd. All rights reserved.