A new synthesis of the ORL-1 antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397) and activity in a calcium mobilization assay

• Published in: Bioorganic & medicinal chemistry Vol. 16; no. 2; pp. 822 - 829
• Main Authors: SMITH, Emilie D, ARIANE VINSON, N, DESONG ZHONG, BERRANG, Bertold D, CATANZARO, Jennifer L, THOMAS, James B, NAVARRO, Hernan A, GILMOUR, Brian P, DESCHAMPS, Jeffrey, CARROLL, F. Ivy
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Science 15.01.2008
• Subjects: Benzimidazoles - chemical synthesis; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Biological and medical sciences; Calcium - metabolism; Crystallography, X-Ray; Humans; Medical sciences; Molecular Conformation; Molecular Structure; Narcotic Antagonists; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Piperidines - chemical synthesis; Piperidines - chemistry; Piperidines - pharmacology; Receptors, Opioid; Stereoisomerism; Chiral synthesis; Calcium; Enantioselectivity; ORL-1 antagonist; Nitrogen heterocycle; In vitro; Biological activity; NOP; Primary alcohol; N/OFQ receptor; J-113397; Piperidine derivatives; Bicyclic compound; Affinity; Ureas; Aromatic compound; Antagonist; Chemical synthesis
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2007.10.023

A new chiral synthesis of the ORL-1 antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (2, J-113397) was developed. J-113397 has a K(e)=0.85nM in an ORL-1 calcium mobilization assay and is 89-, 887-, and 227-fold selective for the ORL-1 receptor relative to the mu, delta, and kappa opioid receptors.