Stereochemical properties of quazepam and its affinity for the GABA A receptor.

Autor: Takano R; Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641Yamazaki, Noda-shi, Chiba 278-8510, Japan., Tanaka R; Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641Yamazaki, Noda-shi, Chiba 278-8510, Japan., Nakamura K; Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641Yamazaki, Noda-shi, Chiba 278-8510, Japan., Tabata H; Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan., Oshitari T; Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan., Natsugari H; Graduate School of Pharmaceutical Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan., Takahashi H; Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641Yamazaki, Noda-shi, Chiba 278-8510, Japan. Electronic address: hide-tak@rs.tus.ac.jp.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2024 Sep 15; Vol. 110, pp. 129854. Date of Electronic Publication: 2024 Jun 22.
DOI: 10.1016/j.bmcl.2024.129854
Abstrakt: C9-methylated quazepam 1 was prepared, and its physicochemical properties were investigated. The atropisomers of 1 were isolated as (a 1 R, a 2 S) and (a 1 S, a 2 R) isomers. Their absolute configurations were determined based on ECD spectra in comparison with those calculated using the time-dependent density functional theory. Preliminary examination of affinity for the GABA A receptor revealed that the (a 1 R, a 2 S) isomer of 1 possessed higher activity than its antipode (a 1 S, a 2 R) isomer. The active configuration of C9-methylated quazepam 1 is the same as that of 1,4-benzodiazepin-2-ones.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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