title: A class of novel N-(1-methyl-β-carboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines: aromatization leaded design, synthesis, in vitro anti-platelet aggregation/in vivo anti-thrombotic evaluation and 3D QSAR analysis.
abstract: High anti-thrombotic activity of aminoacid modified tetrahydro-β-carbolines was generally correlated with a small proximity of the side chain of the aminoacid residue to the carboline-cycle. This paper explored that the aromatization of the tetrahydro-β-carboline-cycle of N-(1-methyl-β-tetrahydrocarboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines leaded to N-(1-methyl-β-carboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines and decreased the proximity of the side chain of the aminoacid residue to the carboline-cycle. The in vitro activities of inhibiting pig platelet aggregation induced by PAF, ADP, and AA, as well as the in vivo anti-thrombotic activities of inhibiting rat thrombosis of these aromatized derivatives were generally higher than that of N-(1-methyl-β-tetrahydrocarboline-3-carbonyl)-N'-(aminoacid-acyl)-hydrazines. The understanding was also obtained from the 3D QSAR analysis.
authors: College of Pharmaceutical Sciences, Capital Medical University, No 10 You An Men Xitoutiao, Beijing 100069, PR China.
authors: Chunyu
authors: C
authors: Li
authors: Xiaoyi
authors: X
authors: Zhang
authors: Ming
authors: M
authors: Zhao
authors: Yuji
authors: Y
authors: Wang
authors: Jianhui
authors: J
authors: Wu
authors: Jiawang
authors: J
authors: Liu
authors: Meiqing
authors: M
authors: Zheng
authors: Shiqi
authors: S
authors: Peng
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D013552:Swine; D013927:Thrombosis / Q000188:drug therapy*
chemical_list: D005343:Fibrinolytic Agents; D006834:Hydrazines; D010975:Platelet Aggregation Inhibitors