title: 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-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.
authors.affiliation: College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yao
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Meiqing
authors.initials: M
authors.lastname: Zheng
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
mesh_terms: D000284:Administration, Oral; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002243:Carbolines / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008297:Male; D023421:Models, Animal; D056004:Molecular Dynamics Simulation; D010974:Platelet Aggregation / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D013927:Thrombosis / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000596:Amino Acids; D002243:Carbolines; D005343:Fibrinolytic Agents; D006834:Hydrazines; C009804:tryptoline