ABSTRACT
An effort with the goal of discovering single-dose, long-lasting (>6â¯months) injectable contraceptives began using levonorgestrel (LNG)-17-ß esters linked to a sulfonamide function purposed as human carbonic anhydrase II (hCA 2) ligands. One single analog from this first series showed noticeably superior anti-ovulatory activity in murine models, and a subsequent structure-activity relationship (SAR, the relationship between a compound's molecular structure and its biological activity) study based on this compound identified a LNG-phenoxyacetic acid ester analog exhibiting longer anti-ovulatory properties using the murine model at 2 and 4â¯mg dose than medroxyprogesterone acetate (MPA). The same ester function linked to etonogestrel (ENG) furnished a compound which inhibited ovulation at 2â¯mg for 60â¯days, the longest duration of all compounds tested at these doses. By comparison, MPA at the same dose inhibited ovulation for 32â¯days.
