N-heterocyclic derived M1 positive allosteric modulators

Bioorg Med Chem Lett. 2010 Feb 15;20(4):1334-7. doi: 10.1016/j.bmcl.2010.01.013. Epub 2010 Jan 11.

Abstract

Replacement of a phenyl ring with N-linked heterocycles in a series of quinolone carboxylic acid M1 positive allosteric modulators was investigated. In particular, a pyrazole derivative exhibited improvements in potency, free fraction, and CNS exposure.

MeSH terms

  • Allosteric Regulation
  • Animals
  • CHO Cells
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Molecular Structure
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Rats
  • Structure-Activity Relationship

Substances

  • Carboxylic Acids
  • Heterocyclic Compounds
  • Pyrazoles
  • Quinolines