title: 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.
authors.affiliation: Instituto de Química Médica (CSIC), Juan de la Cierva 3, E-28006 Madrid, Spain.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: García-López
authors.forename: Rosario
authors.initials: R
authors.lastname: González-Muñiz
authors.forename: Mercedes
authors.initials: M
authors.lastname: Martín-Martínez
authors.forename: Rosario
authors.initials: R
authors.lastname: Herranz
mesh_terms: D000818:Animals; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D010455:Peptides / Q000378:metabolism; D011949:Receptors, Cholecystokinin / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D008024:Ligands; D010455:Peptides; D011949:Receptors, Cholecystokinin