Abstract
To date, J-113397 represents the most potent and selective non peptide NOP receptor antagonist widely used in pharmacological studies. However, the synthesis, purification, and enantiomer separation of this molecule, which contains two chiral centers, is rather difficult and low-yielding. Here, we synthesized and tested a series of simplified J-113397 analogues to investigate the importance of the stereochemistry and the influence of the substituents at position 3 of the piperidine nucleus and on the nitrogen atom of the benzimidazolidinone nucleus. The compound coded as Trap-101, an achiral analogue of J-113397, combines a pharmacological profile similar to that of the parent compound with a practical, high-yielding preparation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzimidazoles / chemical synthesis
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Benzimidazoles / chemistry*
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Benzimidazoles / pharmacology*
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
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Guinea Pigs
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Humans
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In Vitro Techniques
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Male
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Mice
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Models, Molecular
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Narcotic Antagonists*
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Nociceptin Receptor
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Piperidines / chemical synthesis
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Piperidines / chemistry*
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Piperidines / pharmacology*
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Receptors, Opioid / genetics
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Receptors, Opioid / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Stereoisomerism
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Vas Deferens / drug effects
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Vas Deferens / physiology
Substances
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Benzimidazoles
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J 113397
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Narcotic Antagonists
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Piperidines
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Receptors, Opioid
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Recombinant Proteins
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Guanosine 5'-O-(3-Thiotriphosphate)
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Nociceptin Receptor