Name: 2,3-Dihydrospiro[indene-1,4′-piperidine] hydrochloride. The fused heterocycle is formed by combining a benzene ring with a single heterocycle, or two or more single heterocycles. Compound: 2,3-Dihydrospiro[indene-1,4′-piperidine] hydrochloride, is researched, Molecular C13H18ClN, CAS is 96651-85-3, about Efficient design, synthesis and structure-activity relationship studies of 1-(3′-substituted propyl)-4-arylpiperidines as non-peptide antagonists of nociceptin/orphanin FQ receptor: biological activities, metabolic stabilities and hERG channel bindings. Author is Hayashi, Shigeo; Ohashi, Katsuyo; Nakata, Eriko; Emoto, Chie.
Nociceptin/orphanin FQ (N/OFQ) is an endogenous heptadecapeptide that is a metabolite of precursor polypeptide (prepro-N/OFQ), and N/OFQ peptide (NOP) receptor (or opioid-receptor-like-1 receptor) is a G-protein-coupled receptor (GPCR) that is distinct from classical opioid peptide receptors, whereas the receptors share high sequence-similarities. As well, [35S]-guanosine 5′-(γ-thiotriphosphate) binding that was stimulated by N/OFQ-NOP receptor binding was not affected by various GPCR antagonists including opioid receptor antagonists. N/OFQ and NOP receptor are located in the spinal cord, the peripheral nervous systems and other peripheral tissues that are related to pain-inhibitory signal transmissions, and in the corticolimbic regions that are involved in the integration of the emotional components. Indeed, potent and selective new-class NOP receptor agonists as systemically potent analgesic against neuropathic pain and as orally potent anxiolytic with resp. unique safe-profiles have been discovered in our studies. Besides, the blockade of N/OFQ actions via N/OFQ-NOP receptor system has been displayed as anti-depression effect, anti-hyperplasia effect and anti-hypotension effect in animal model studies, which might show potential utilities of NOP receptor antagonists to modulate/attenuate N/OFQ activity for regulation of human physiologies in pharmacol. and clin. viewpoints. Hence, the design, synthesis, structure-activity relationship in vitro and structure-metabolic stability relationship in vitro of various 1-(3′-substituted propyl)-4-arylpiperidine derivatives, e.g., I, were investigated to seek and identify potent and selective new-class NOP receptor antagonists with metabolic stabilities and little hERG ion channel binding affinities by multi-viewpoint and integrated drug-design strategies, with clarifying structural features and physicochem. properties as key factors for the purposes. The unique and efficient studies, and their exclusive results and findings for the analogs are described herein.
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