Stereochemical properties of quazepam and its affinity for the GABA<sub>A</sub> receptor.

Takano, Ryota; Tanaka, Ryoko; Nakamura, Kayo; Tabata, Hidetsugu; Oshitari, Tetsuta; Natsugari, Hideaki; Takahashi, Hideyo

Stereochemical properties of quazepam and its affinity for the GABA_A receptor.

Takano, Ryota; Tanaka, Ryoko; Nakamura, Kayo; Tabata, Hidetsugu; Oshitari, Tetsuta; Natsugari, Hideaki; Takahashi, Hideyo.

Afiliação

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.

Bioorg Med Chem Lett ; 110: 129854, 2024 Sep 15.

Article em En | MEDLINE | ID: mdl-38914347

ABSTRACT

ABSTRACT

C9-methylated quazepam 1 was prepared, and its physicochemical properties were investigated. The atropisomers of 1 were isolated as (a1R, a2S) and (a1S, a2R) 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 GABAA receptor revealed that the (a1R, a2S) isomer of 1 possessed higher activity than its antipode (a1S, a2R) isomer. The active configuration of C9-methylated quazepam 1 is the same as that of 1,4-benzodiazepin-2-ones.

Assuntos

Receptores de GABA-A; Receptores de GABA-A/metabolismo; Receptores de GABA-A/química; Estereoisomerismo; Relação Estrutura-Atividade; Estrutura Molecular; Humanos; Benzodiazepinonas/química; Benzodiazepinonas/farmacologia; Benzodiazepinonas/síntese química; Teoria da Densidade Funcional

Palavras-chave

Atropisomer; Axial chirality; Benzodiazepine; GABA(A) receptor; Quazepam

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de GABA-A Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

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