Investigation of selective retinoic acid receptor alpha antagonist ER-50891 and related analogs for male contraception.
Arch Pharm (Weinheim)
; 356(7): e2300031, 2023 Jul.
Article
em En
| MEDLINE
| ID: mdl-37154197
ABSTRACT
Retinoic acid receptor alpha (RARα) antagonist ER-50891 and 15 analogs were prepared and tested in vitro for potency and selectivity at RARα, RARß, and RARγ using transactivation assays. Minor modifications to the parent molecule such as the introduction of a C4 tolyl group in place of the C4 phenyl group on the quinoline moiety slightly increased the RARα selectivity but larger substituents significantly decreased the potency. Replacement of the pyrrole moiety of ER-50891 with triazole, amides, or a double bond produced inactive compounds. ER-50891 was found to be stable in male mouse liver microsomes and was tested in male mice to assess its effects on spermatogenesis. Characteristic, albeit modest and transient, effects on spermatogenesis were observed.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anticoncepção
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article