SAR study of 2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepines as progesterone receptor agonists

Bioorg Med Chem Lett. 2008 Feb 15;18(4):1461-7. doi: 10.1016/j.bmcl.2007.12.065. Epub 2007 Dec 28.

Abstract

We have developed a new class of progesterone receptor agonists having a tetracyclic dibenzo-oxazepine structure 1. In this paper, the synthesis and structure-activity relationships of this new class are described. This work led to the identification of potent progesterone agonists up to 1 nM activity. Substitution at positions 6, 7 and 1 has proven to be crucial for activity, indicating that probably these positions are involved in important interactions with the receptor.

MeSH terms

  • Acetamides
  • Binding Sites
  • Fluoroacetates
  • Models, Molecular
  • Oxazepines / chemistry*
  • Oxazepines / pharmacology*
  • Progesterone / chemistry
  • Receptors, Progesterone / agonists*
  • Structure-Activity Relationship
  • Trifluoroacetic Acid / chemistry

Substances

  • Acetamides
  • Fluoroacetates
  • Oxazepines
  • Receptors, Progesterone
  • trifluoroacetamide
  • Progesterone
  • Trifluoroacetic Acid