4,5-Disubstituted cis-pyrrolidinones as inhibitors of type II 17beta-hydroxysteroid dehydrogenase. Part 3. Identification of lead candidate

Bioorg Med Chem Lett. 2006 Sep 15;16(18):4965-8. doi: 10.1016/j.bmcl.2006.06.041. Epub 2006 Jun 27.

Abstract

A series of 4,5-disubstituted cis-pyrrolidinones was investigated as inhibitors of 17beta-HSD II for the treatment of osteoporosis. Biochemical data for several compounds are given. Compound 42 was selected as the lead candidate.

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
  • 17-Hydroxysteroid Dehydrogenases / metabolism
  • Animals
  • Cell Line
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Macaca fascicularis
  • Pyrrolidinones / chemical synthesis
  • Pyrrolidinones / chemistry*
  • Pyrrolidinones / pharmacology*
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry*
  • Thiophenes / pharmacology*

Substances

  • 5-(15-hydroxy(5-(3-pyridyl)(2-thienyl))methyl)-1-methyl-4-phenylpyrrolidin-2-one
  • Enzyme Inhibitors
  • Pyrrolidinones
  • Thiophenes
  • 17-Hydroxysteroid Dehydrogenases
  • 3 (or 17)-beta-hydroxysteroid dehydrogenase