Identification of an achiral analogue of J-113397 as potent nociceptin/orphanin FQ receptor antagonist
| Autor: | Severo Salvadori, Samantha Rubini, Christopher P. Hebbes, Remo Guerrini, Claudio Trapella, Domenico Regoli, Giulia Fanton, David G. Lambert, Girolamo Calo, Barbara Spagnolo, Giacomo Carrà, John McDonald, Laura Piccagli |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Male
Models Molecular NOP receptor Stereochemistry medicine.drug_class Narcotic Antagonists Guinea Pigs Clinical Biochemistry NOP Pharmaceutical Science Stereoisomerism In Vitro Techniques Nociceptin/orphanin FQ Non peptide antagonists J-113397 Mouse vas deferens assay Structure–activity study Biochemistry Chemical synthesis Nociceptin Receptor NO Mice chemistry.chemical_compound Vas Deferens Piperidines Drug Discovery medicine Animals Humans Molecular Biology Organic Chemistry Antagonist Receptor antagonist Combinatorial chemistry Recombinant Proteins medicine.anatomical_structure chemistry Guanosine 5'-O-(3-Thiotriphosphate) Receptors Opioid Molecular Medicine Benzimidazoles Piperidine Enantiomer Nucleus |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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