Pyrazole CCK(1) receptor antagonists. Part 1: Solution-phase library synthesis and determination of Free-Wilson additivity

Bioorg Med Chem Lett. 2006 Jan 1;16(1):72-6. doi: 10.1016/j.bmcl.2005.09.048. Epub 2005 Oct 19.

Abstract

High throughput screening revealed compound 1 as a potent antagonist of the CCK(1) receptor. Evaluation of the CCK(1) SAR in a series of these diarylpyrazole antagonists was conducted in a matrix synthesis format revealing additive (Free-Wilson) and non-additive SAR. This use of additive QSAR modeling in conjunction with combinatorial libraries represents a unique approach to the evaluation of SAR interactions between the variables of any combinatorial matrix.

MeSH terms

  • Chemistry, Pharmaceutical / methods*
  • Cholecystokinin / chemistry
  • Combinatorial Chemistry Techniques
  • Humans
  • Hydrogen-Ion Concentration
  • Models, Chemical
  • Models, Statistical
  • Peptide Library
  • Pharmaceutical Preparations / chemistry
  • Protein Binding
  • Pyrazoles / chemistry*
  • Receptor, Cholecystokinin A / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Peptide Library
  • Pharmaceutical Preparations
  • Pyrazoles
  • Receptor, Cholecystokinin A
  • Cholecystokinin