Basic Research on Amide-based Axial Chirality and Development to Medicinal Chemistry

2016 Fiscal Year Final Research Report

• Project/Area Number: 25460154
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Teikyo University
• Principal Investigator: Natsugari Hideaki 帝京大学, 医療共通教育研究センター, 教授 (00334334)
• Co-Investigator(Renkei-kenkyūsha): TABATA HIDETSUGU 帝京大学, 薬学部, 講師 (80445634)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 軸不斉 / 立体化学 / キラリティー / ベンゾジアゼピン / バソプレシン

Outline of Final Research Achievements

Aryl amides and anilides, which exist in many biologically active molecules as parts of the pharmacophore, possess sp2-sp2 atropisomerism based on the aryl-amide axis. Although often overlooked, such atropisomerisms are latent in many organic molecules. When exerting biological activity, the receptors and enzymes should recognize the specific conformation of themolecules. In this study, conformational change of the benzo-fused seven-membered-ring nitrogen heterocycles, which have been used as important core structures of various biologically active molecules, was studied in relation to the biological activity. Especially, the active form of the tolvaptan-type vasopressin antagonist was examined in detail to reveal the axial chirality plays a more important role than the central chirality at C5 in receptor recognition. The study also revealed that N-sulfonyl-1,5-benzodiazepines also possess sp2-sp2 atropisomerism based on the aryl-N(SO2) axis.

Free Research Field

有機合成化学、医薬品化学