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Updated: Apr 25, 2026

Intracranial Pharmacotherapy and Pain Assays in Rodents
Published on: April 9, 2019
Discovery of a Potent Analgesic NOP and Opioid Receptor Agonist: Cebranopadol
Stefan Schunk1, Klaus Linz1, Claudia Hinze1
1Departments of Medicinal Chemistry, Preclinical Drug Safety, Molecular Pharmacology, Pain Pharmacology, Pharmacokinetics, and Discovery Informatics, Global Drug Discovery, Grünenthal Innovation, Grünenthal GmbH , D-52099 Aachen, Germany.
Abstract:
In a previous communication, our efforts leading from 1 to the identification of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amine 2a as analgesic NOP and opioid receptor agonist were disclosed and their favorable in vitro and in vivo pharmacological properties revealed. We herein report our efforts to further optimize lead 2a, toward trans-6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'(3'H)-pyrano[3,4-b]indol]-4-amine (cebranopadol, 3a), which is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.
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