Simple Synthesis of a Heterocyclophane Exhibiting Anti-c-Met Activity by Acting as a Hatch Blocking Access to the Active Site*.

Autor: Takimoto T; Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Minatojima, chuo-ku, Kobe, 650-8586, Japan., Sasaki H; Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Minatojima, chuo-ku, Kobe, 650-8586, Japan., Tsue H; Graduate School of Human and Environmental Studies, Kyoto University, Yoshida Nihonmatsu-cho, Sakyo-ku, Kyoto, 606-8501, Japan., Takahashi H; Graduate School of Human and Environmental Studies, Kyoto University, Yoshida Nihonmatsu-cho, Sakyo-ku, Kyoto, 606-8501, Japan., MacKerell AD Jr; Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Baltimore, 20 Penn Street, Baltimore, Maryland, 21201, USA., Nakamura A; Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Minatojima, chuo-ku, Kobe, 650-8586, Japan., Nakano K; Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Minatojima, chuo-ku, Kobe, 650-8586, Japan., Okazaki E; Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Minatojima, chuo-ku, Kobe, 650-8586, Japan., Betsuyaku T; Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Minatojima, chuo-ku, Kobe, 650-8586, Japan., Tachibana R; Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Minatojima, chuo-ku, Kobe, 650-8586, Japan., Hioki K; Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Minatojima, chuo-ku, Kobe, 650-8586, Japan., Yoluk O; Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Baltimore, 20 Penn Street, Baltimore, Maryland, 21201, USA., Jo S; SilcsBio LLC, 20 Penn Street, Baltimore, Maryland, 21201, USA.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2021 Jan 21; Vol. 27 (5), pp. 1648-1654. Date of Electronic Publication: 2020 Dec 15.
DOI: 10.1002/chem.202001382
Abstrakt: A simple approach to the synthesis of heterocyclophane consisting of two 4,4'-bithiazoles has been developed in mild conditions. The heterocyclophane with two short chains was conveniently prepared by Hantzsch thiazoles synthesis using the reaction of 3-tert-butoxycarbonyl-3-azapentanethiocarboxamide with 1,4-dibromobutane-2,3-dione in methanol under reflux for only 15 min. Amino groups at the linkers of this heterocyclophane can be functionalized to give acylated and carbamate derivatives. Their properties as protein kinase inhibitors were investigated, and one of the heterocyclophanes exhibited specific anti-activity for c-mesenchymal epithelial transition factor (IC 50 =603 nm), among seven types of protein kinases investigated. The computational site identification by ligand competitive saturation method was used to determine why the one heterocyclophane exhibited strong anti-activity for c-mesenchymal epithelial transition factor.
(© 2020 Wiley-VCH GmbH.)
Databáze: MEDLINE
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