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

Eric Lattmann*, Harjit Singh, Yodchai Boonprakob, Pornthip Lattmann, Jintana Sattayasai

*Corresponding author for this work

Research output: Contribution to journalArticle

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 CCK 1 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 CCK 1 for the CCK 1 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. © 2006 The Authors.

Original languageEnglish
Pages (from-to)393-401
Number of pages9
JournalJournal of Pharmacy and Pharmacology
Volume58
Issue number3
DOIs
Publication statusPublished - Mar 2006

Fingerprint

Cholecystokinin
Amides
Antidepressive Agents
Cholecystokinin A Receptor
Cholecystokinin Receptors
Ligands
Anti-Anxiety Agents
Structure-Activity Relationship
Inhibitory Concentration 50
Pharmacology
diphenyl
indole

Cite this

Lattmann, Eric ; Singh, Harjit ; Boonprakob, Yodchai ; Lattmann, Pornthip ; Sattayasai, Jintana. / Synthesis and evaluation of N-(3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-1H-indole-carboxamides as cholecystokinin antagonists. In: Journal of Pharmacy and Pharmacology. 2006 ; Vol. 58, No. 3. pp. 393-401.
@article{24d640be96d14b8cb69c0b54a37170d1,
title = "Synthesis and evaluation of N-(3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-1H-indole-carboxamides as cholecystokinin antagonists",
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 CCK 1 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 CCK 1 for the CCK 1 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. {\circledC} 2006 The Authors.",
author = "Eric Lattmann and Harjit Singh and Yodchai Boonprakob and Pornthip Lattmann and Jintana Sattayasai",
year = "2006",
month = "3",
doi = "10.1211/jpp.58.3.0015",
language = "English",
volume = "58",
pages = "393--401",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
publisher = "Pharmaceutical Press",
number = "3",

}

Synthesis and evaluation of N-(3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-1H-indole-carboxamides as cholecystokinin antagonists. / Lattmann, Eric; Singh, Harjit; Boonprakob, Yodchai; Lattmann, Pornthip; Sattayasai, Jintana.

In: Journal of Pharmacy and Pharmacology, Vol. 58, No. 3, 03.2006, p. 393-401.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis and evaluation of N-(3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-1H-indole-carboxamides as cholecystokinin antagonists

AU - Lattmann, Eric

AU - Singh, Harjit

AU - Boonprakob, Yodchai

AU - Lattmann, Pornthip

AU - Sattayasai, Jintana

PY - 2006/3

Y1 - 2006/3

N2 - 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 CCK 1 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 CCK 1 for the CCK 1 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. © 2006 The Authors.

AB - 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 CCK 1 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 CCK 1 for the CCK 1 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. © 2006 The Authors.

UR - http://www.scopus.com/inward/record.url?scp=33644782623&partnerID=8YFLogxK

UR - http://onlinelibrary.wiley.com/doi/10.1211/jpp.58.3.0015/abstract

U2 - 10.1211/jpp.58.3.0015

DO - 10.1211/jpp.58.3.0015

M3 - Article

C2 - 16536908

VL - 58

SP - 393

EP - 401

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 3

ER -