A tissue-selective nonsteroidal progesterone receptor modulator: 7,9-difluoro-5-(3-methylcyclohex-2-enyl)-2,2,4-trimethyl-1,2-dihydrochromeno[3,4-f]quinoline

  • J Med Chem. 2008 Jul 10;51(13):3696-9. doi: 10.1021/jm8004256.
Bijan Pedram  1 ,  Arjan van Oeveren ,  Dale E Mais ,  Keith B Marschke ,  Pieter M Verbost ,  Marinus B Groen ,  Lin Zhi
Affiliations
  • 1. Discovery Research, Ligand Pharmaceuticals Inc., 10275 Science Center Drive, San Diego, California 92121, USA.
PMID: 18553958 DOI: 10.1021/jm8004256
Abstract

The Progesterone Receptor plays an important role in the female reproductive system. Here we describe the discovery of a new selective Progesterone Receptor Modulator (SPRM). In rats, the lead compound, 7,9-difluoro-5-(3-methylcyclohex-2-enyl)-2,2,4-trimethyl-1,2-dihydrochromeno[3,4- f]quinoline ( 5c), inhibited ovulation and showed full efficacy in uterine and vaginal tissue but was a mixed partial agonist/antagonist in breast tissue. The compound also suppressed ovulation in monkeys, but in contrast to currently approved steroidal PR agonists, it did not suppress estradiol levels.