Synthesis and SAR of N-(4-(4-alklylpiperazin-1-yl)phenyl)benzamides as muscarinic acetylcholine receptor subtype 1 (M1) anatgonists

Bioorg Med Chem Lett. 2010 Apr 1;20(7):2174-7. doi: 10.1016/j.bmcl.2010.02.041. Epub 2010 Feb 13.

Abstract

This Letter describes the synthesis and SAR, developed through an iterative analog library approach, of a novel series of selective M(1) mAChR antagonists, based on an N-(4-(4-alkylpiperazin-1-yl)phenyl)benzamide scaffold for the potential treatment of Parkinson's disease, dystonia and other movement disorders. Compounds in this series possess M(1) antagonist IC(50)s in the 350 nM to >10 microM range with varying degrees of functional selectivity versus M(2)-M(5).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Benzamides / chemical synthesis
  • Benzamides / chemistry*
  • Benzamides / pharmacology*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Dystonia / drug therapy
  • Humans
  • Mice
  • Molecular Sequence Data
  • Parkinson Disease / drug therapy
  • Receptor, Muscarinic M1 / antagonists & inhibitors*
  • Receptor, Muscarinic M1 / chemistry
  • Receptor, Muscarinic M1 / metabolism*
  • Structure-Activity Relationship

Substances

  • Benzamides
  • Receptor, Muscarinic M1