Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Analgesics / chemical synthesis
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Analgesics / chemistry*
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Analgesics / pharmacology
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Animals
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CHO Cells
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Calcium / metabolism
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Cricetulus
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Cyclohexanecarboxylic Acids / chemical synthesis
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Cyclohexanecarboxylic Acids / chemistry*
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Cyclohexanecarboxylic Acids / pharmacology
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Drug Partial Agonism
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry*
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Pyrazoles / pharmacology
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Radioligand Assay
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Rats
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Receptors, Neurotensin / agonists*
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Receptors, Neurotensin / antagonists & inhibitors
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Structure-Activity Relationship
Substances
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1-(((1-(4-fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl)carbonyl)amino)cyclohexanecarboxylic acid
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Analgesics
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Cyclohexanecarboxylic Acids
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Ntsr2 protein, rat
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Pyrazoles
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Receptors, Neurotensin
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Calcium