Heterobiaryl and heterobiaryl ether derived M5 positive allosteric modulators

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5617-22. doi: 10.1016/j.bmcl.2010.08.042. Epub 2010 Aug 12.

Abstract

This Letter describes a chemical lead optimization campaign directed at VU0238429, the first M(5)-preferring positive allosteric modulator (PAM), discovered through analog work around VU0119498, a pan G(q) mAChR M(1), M(3), M(5) PAM. An iterative parallel synthesis approach was employed to incorporate basic heterocycles to improve physiochemical properties.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Allosteric Regulation
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Ethers / chemical synthesis
  • Ethers / chemistry*
  • Ethers / pharmacology
  • Heterocyclic Compounds / chemistry*
  • High-Throughput Screening Assays
  • Humans
  • Receptors, Muscarinic / chemistry
  • Receptors, Muscarinic / metabolism
  • Structure-Activity Relationship

Substances

  • Ethers
  • Heterocyclic Compounds
  • Receptors, Muscarinic