Kyzer, Jillian2020-02-262020-02-262018-12https://hdl.handle.net/11299/211772University of Minnesota Ph.D. dissertation. December 2018. Major: Medicinal Chemistry. Advisor: Gunda Georg. 1 computer file (PDF); xiv, 204 pages.There have been significant advances in female contraceptive methods since the invention of the birth control pill in the 1960s. However, little progress has been made in the area of male contraceptive methods. Current approved forms of contraceptive options are either temporary barrier methods (such as condoms) or permanent surgical sterilization. Through the efforts by the National Institute of Child Health and Human Development, new strategies are being developed which would provide men with greater control over their reproductive lives. While much of the former research has focused on hormonal methods, we hypothesized that a non-hormonal method would be more tolerated. Previous research has pointed to the Retinoic Acid Receptor alpha (RAR-alpha) as a viable target for establishing reversible male infertility, as a knockout model of RAR-alpha produced spermatogenic defects in otherwise healthy mice. These spermatogenic defects were observed in mice deficient in Vitamin A (the precursor to retinoic acid) as well as mice that were administered BMS-189453, an antagonist of RAR-alpha, RAR-beta, and RAR-gamma. Given these promising studies, we hypothesized that the development of a bioavailable RAR-alpha antagonist would impart reversible male infertility. We designed and synthesized a variety of retinoids modeled around two previously developed compounds, BMS-189532 and ER-50891in order to improve the bioavailability of these RAR-alpha antagonists. The retinoids were subsequently evaluated for activity at RAR-alpha, RAR-beta, and RAR-gamma.encontraceptionretinoic acidThesis or Dissertation