Esters of levonorgestrel and etonogestrel intended as single, subcutaneous-injection, long-lasting contraceptives

Frederick A. Meece, Gulzar Ahmed, Hareesh Nair, Bindu Santhamma, Rajeshwar R. Tekmal, Chumang Zhao, Nicole E. Pollok, Julia Lara, Ze'ev Shaked, Klaus Nickisch

Research output: Contribution to journalArticlepeer-review

Abstract

An effort with the goal of discovering single-dose, long-lasting (>6 months) injectable contraceptives began using levonorgestrel (LNG)-17-β 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 4 mg dose than medroxyprogesterone acetate (MPA). The same ester function linked to etonogestrel (ENG) furnished a compound which inhibited ovulation at 2 mg for 60 days, the longest duration of all compounds tested at these doses. By comparison, MPA at the same dose inhibited ovulation for 32 days.

Original languageEnglish (US)
Pages (from-to)47-56
Number of pages10
JournalSteroids
Volume137
DOIs
StatePublished - Sep 2018

Keywords

  • Etonogestrel
  • Injectable contraception
  • Levonorgestrel
  • MPA
  • Prodrug

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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