Synthesis and evaluation of N-(3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-1H-indole-carboxamides as cholecystokinin antagonists

The Journal of Pharmacy and Pharmacology
Eric LattmannJintana Sattayasai

Abstract

The structure-activity relationship optimization of the pyrazoline template 3a resulted in novel 3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-indole carboxamides 4a-4e. These non-peptidal CCK ligands have been shown to act as potent CCK1 ligands in a [125]I-CCK-8 receptor binding assay. The best amides (4c and 4d) of this series displayed an IC50 of 20/25 nM for the CCK1 receptor. In a subsequent in-vivo evaluation using various behaviour pharmacological assays, an anxiolytic effect of these novel 3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-indole carboxamides was found at high doses in the elevated plus-maze. In the despair swimming test, a model for testing antidepressants, an ED50 of 0.33/0.41 mg kg(-1) was determined for amide 4c/4d and the antidepressant effect had a magnitude comparable to desimipramine.

References

Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J HughesG N Woodruff
Feb 1, 1990·Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie·J BradwejnG Meterissian
Jul 1, 1990·Trends in Pharmacological Sciences·S Ravard, C T Dourish
Mar 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·B CharpentierB P Roques
Feb 1, 1983·Australian and New Zealand Journal of Medicine·M L FriedlanderM H Tattersall
Mar 1, 1983·Physiology & Behavior·J M Walker, W C Dixon
Dec 1, 1995·Chemical & Pharmaceutical Bulletin·M SatohK Murase
Jan 6, 1999·Journal of Pharmaceutical Sciences·R A Blouin, G W Warren
Jun 25, 2002·The Journal of Pharmacy and Pharmacology·Eric LattmannMichael Offel

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Citations

Mar 19, 2013·Archives of Pharmacal Research·Azza T Taher, Lamia W Mohammed
Apr 5, 2018·Current Pain and Headache Reports·Alan David KayeKenneth F Mancuso
May 5, 2016·Archiv der Pharmazie·Eric LattmannPornthip Lattmann

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