Stimulation of cortical bone formation with thienopyrimidine based inhibitors of Notum Pectinacetylesterase

Bioorg Med Chem Lett. 2016 Mar 15;26(6):1525-1528. doi: 10.1016/j.bmcl.2016.02.021. Epub 2016 Feb 10.

Abstract

A group of small molecule thienopyrimidine inhibitors of Notum Pectinacetylesterase are described. We explored both 2-((5,6-thieno[2,3-d]pyrimidin-4-yl)thio)acetic acids and 2-((6,7-thieno[3,2-d]pyrimidin-4-yl)thio)acetic acids. In both series, highly potent, orally active Notum Pectinacetylesterase inhibitors were identified.

Keywords: Femur cortical bone thickness; Notum Pectinacetylesterase; Osteoporosis; SAR; Thienopyrimidine.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Esterases / antagonists & inhibitors*
  • Esterases / metabolism
  • Femur / anatomy & histology
  • Femur / drug effects*
  • Femur / growth & development
  • Humans
  • Mice
  • Molecular Structure
  • Osteogenesis / drug effects*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Pyrimidines
  • thienopyrimidine
  • Esterases
  • Notum protein, human
  • Notum protein, mouse