Pyrazole CCK1 receptor antagonists. Part 1: Solution-phase library synthesis and determination of Free–Wilson additivity

https://doi.org/10.1016/j.bmcl.2005.09.048Get rights and content

Abstract

High throughput screening revealed compound 1 as a potent antagonist of the CCK1 receptor. Evaluation of the CCK1 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.

Section snippets

Acknowledgments

We thank Jiejun Wu and Heather McAllister for analytical chemistry support.

References and notes (11)

  • A.C. Ivy et al.

    Am. J. Physiol.

    (1928)
  • V. Mutt et al.

    Biochem. J.

    (1971)
  • R. Herranz

    Med. Res. Rev.

    (2003)
    P. Tullio et al.

    Expert Opin. Investig. Drugs

    (2000)
  • G. Varga

    Curr. Opin. Investig. Drugs

    (2002)
  • W.V. Murray et al.

    J. Heterocyclic Chem.

    (1990)
There are more references available in the full text version of this article.

Cited by (27)

  • Pyrazole CCK1 receptor antagonists

    2007, Drug Discovery Today
View all citing articles on Scopus
View full text