Retinoic acid receptor alpha (RARα) antagonist ER-50891 and 15 analogs were prepared and tested in vitro for potency and selectivity at RARα, RARβ, 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.
Bibliographical noteFunding Information:
Jillian L. Kyzer acknowledges support from NIH predoctoral training grant 5 T32 GM008700 and Md Abdullah Al Noman acknowledges a predoctoral fellowship from the Male Contraceptive Initiative. This work was supported by NICHD grants 1 U01 HD076542, P50 HD093540, and NICHD contract HHSN275201300017C.
© 2023 Deutsche Pharmazeutische Gesellschaft.
- retinoic acid receptor alpha
- transactivation assays
PubMed: MeSH publication types
- Journal Article