Synthesis and structure-activity relationship of novel 6-aryl-1,4-dihydrobenzo[d][1,3]oxazine-2-thiones as progesterone receptor modulators leading to the potent and selective nonsteroidal progesterone receptor agonist tanaproget

J Med Chem. 2005 Aug 11;48(16):5092-5. doi: 10.1021/jm050358b.

Abstract

Tanaproget represents a potential first-in-class nonsteroidal PR agonist for contraception with improved safety and side effect profiles versus currently available steroidal oral contraceptives. Additional SAR, biological activity, and structural information from a tanaproget/hPR-LBD (hPR-LBD = human progesterone receptor ligand binding domain) cocrystal structure will also be presented.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Area Under Curve
  • Benzoxazines / chemical synthesis*
  • Benzoxazines / chemistry
  • Benzoxazines / pharmacology
  • Binding, Competitive
  • Cell Line, Tumor
  • Contraceptive Agents, Female / chemical synthesis
  • Contraceptive Agents, Female / chemistry
  • Contraceptive Agents, Female / pharmacology
  • Decidua / drug effects
  • Decidua / metabolism
  • Female
  • Half-Life
  • Humans
  • In Vitro Techniques
  • Ligands
  • Molecular Structure
  • Oxazines / chemical synthesis*
  • Oxazines / chemistry
  • Oxazines / pharmacology
  • Protein Structure, Tertiary
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Progesterone / agonists*
  • Receptors, Progesterone / antagonists & inhibitors
  • Receptors, Progesterone / chemistry
  • Structure-Activity Relationship
  • Thiones / chemical synthesis*
  • Thiones / chemistry
  • Thiones / pharmacology

Substances

  • Benzoxazines
  • Contraceptive Agents, Female
  • Ligands
  • Oxazines
  • Pyrroles
  • Receptors, Progesterone
  • Thiones
  • tanoproget
  • Alkaline Phosphatase