Strategies for design of non peptide CCK1R agonist/antagonist ligands.

Abstract:

:This review mainly covers last five year literature on CCK1R agonists and antagonists. These CCK1R ligands have been found following the two usual and complementary strategies for drug discovery: rational design based on structure activity relationships on the CCK-7 and CCK-4 peptide sequences of the endogenous ligands and random screening of diverse compounds, followed by hit optimization. The first group includes: chimeric bifunctional opioid/CCK peptides, designed as opioid agonists with balanced CCK1R/CCK2R antagonist activity for the treatment of neuropathic pain, antagonist and agonist dipeptoids, and 1,3-dioxoperhydropyrido[1,2-c]pyrimidine- and anthranilic acid-based antagonists. Among the ligands derived from random screening, a few new 1,4-benzodiazepine-, 1,5-benzodiazepine-, and five member ring heterocycle-based CCK1R ligands have been reported. Finally, taking into account the importance of receptor mapping studies for ligand optimization and future precise de novo receptor structure-based design of new selective and more effective ligands, the most significant conclusions of these studies have also been reviewed.

journal_name

Curr Top Med Chem

authors

García-López MT,González-Muñiz R,Martín-Martínez M,Herranz R

doi

10.2174/156802607780960537

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

1180-94

issue

12

eissn

1568-0266

issn

1873-4294

journal_volume

7

pub_type

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