6-Aryl-1,4-dihydro-benzo[d][1,3]oxazin- 2-ones: a novel class of potent, selective, and orally active nonsteroidal progesterone receptor antagonists

J Med Chem. 2002 Sep 26;45(20):4379-82. doi: 10.1021/jm025555e.

Abstract

Novel 6-aryl-1,4-dihydro-benzo[d][1,3]oxazin-2-ones were synthesized and tested as progesterone receptor (PR) antagonists. These compounds were potent and showed good selectivity for PR over other steroid receptors such as the glucocorticoid and androgen receptors (e.g., greater than 80-fold selectivity at PR for 4h). Numerous 6-aryl benzoxazinones (e.g., 4h-j) were active orally in the uterine decidualization and component C3 assays in the rats. In these in vivo models,4h had potencies comparable to mifepristone.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Alkaline Phosphatase / metabolism
  • Animals
  • Biological Availability
  • Decidua / drug effects
  • Female
  • Hormone Antagonists / chemical synthesis*
  • Hormone Antagonists / chemistry
  • Hormone Antagonists / pharmacology
  • Humans
  • Luciferases / genetics
  • Mifepristone / pharmacology
  • Ovariectomy
  • Oxazines / chemical synthesis*
  • Oxazines / chemistry
  • Oxazines / pharmacology
  • Rats
  • Receptors, Progesterone / agonists
  • Receptors, Progesterone / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Hormone Antagonists
  • Oxazines
  • Receptors, Progesterone
  • Mifepristone
  • Luciferases
  • Alkaline Phosphatase