Identification of 1-({[1-(4-Fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)cyclohexane Carboxylic Acid as a Selective Nonpeptide Neurotensin Receptor Type 2 Compound | Zendy

James B. Thomas | Zendy; Angela M. Giddings | Zendy; Robert W. Wiethe | Zendy; O. Srinivas | Zendy; Keith R. Warner | Zendy; Philippe Sarret | Zendy; Louis Gendron | Zendy; JeanMichel Longpré | Zendy; Yanan Zhang | Zendy; Scott P. Runyon | Zendy; Brian P. Gilmour | Zendy

Open Access

Identification of 1-({[1-(4-Fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)cyclohexane Carboxylic Acid as a Selective Nonpeptide Neurotensin Receptor Type 2 Compound

Author(s) -

James B. Thomas,

Angela M. Giddings,

Robert W. Wiethe,

O. Srinivas,

Keith R. Warner,

Philippe Sarret,

Louis Gendron,

JeanMichel Longpré,

Yanan Zhang,

Scott P. Runyon,

Brian P. Gilmour

Publication year - 2014

Publication title -

journal of medicinal chemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.01

H-Index - 261

eISSN - 1520-4804

pISSN - 0022-2623

DOI - 10.1021/jm5003843

Subject(s) - neurotensin , chemistry , cyclohexane , carboxylic acid , peptide , receptor , stereochemistry , amino acid , chemical synthesis , pharmacology , biochemistry , in vitro , neuropeptide , medicine , organic chemistry

Compounds active at neurotensin receptors (NTS1 and NTS2) exert analgesic effects on different types of nociceptive modalities, including thermal, mechanical, and chemical stimuli. The NTS2 preferring peptide JMV-431 (2) and the NTS2 selective nonpeptide compound levocabastine (6) have been shown to be effective in relieving the pain associated with peripheral neuropathies. With the aim of identifying novel nonpeptide compounds selective for NTS2, we examined analogues of SR48692 (5a) using a FLIPR calcium assay in CHO cells stably expressing rat NTS2. This led to the discovery of the NTS2 selective nonpeptide compound 1-({[1-(4-fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)cyclohexane carboxylic acid (NTRC-739, 7b) starting from the nonselective compound 5a.

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