Chromenopyrazole, a Versatile Cannabinoid Scaffold with in Vivo Activity in a Model of Multiple Sclerosis
Year: 2016
Type: article
Abstract: A combination of molecular modeling and structure-activity relationship studies has been used to fine-tune CB2 selectivity in the chromenopyrazole ring, a versatile CB1/CB2 cannabinoid scaffold. Thus, a series of 36 new derivatives covering a wide range of structural diversity has been synthesized, and docking studies have been performed for some of them. Biological evaluation of the new compounds includes, among others, cannabinoid binding assays, functional studies, and surface plasmon resonance measurements. The most promising compound [43 (PM226)], a selective and potent CB2 agonist isoxazole derivative, was tested in the acute phase of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), a well-established animal model of primary progressive multiple sclerosis. Compound 43 dampened neuroinflammation by reducing microglial activation in the TMEV.
Source: Journal of Medicinal Chemistry
Institutions: Consejo Superior de Investigaciones Científicas, Instituto de Química Médica, Universidad Complutense de Madrid, Biomedical Research Networking Center on Neurodegenerative Diseases, Centro de Investigación Biomédica en Red, Instituto Ramón y Cajal de Investigación Sanitaria, Universitat de Barcelona, University of North Carolina at Greensboro, Instituto Cajal
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2431558107