Discovery of a Biased Allosteric Modulator for Cannabinoid 1 Receptor: Preclinical Anti-Glaucoma Efficacy

We apply the magic methyl effect to improve the potency/efficacy of GAT211, the prototypic 2-phenylindole-based cannabinoid type-1 receptor (CB1R) agonist-positive allosteric modulator (ago-PAM). Introducing a methyl group at the a-position of nitro group generated two diastereomers, the greater pot...

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Bibliographic Details
Published in:	Journal of medicinal chemistry Vol. 64; no. 12; pp. 8104 - 8126
Main Authors:	Garai, Sumanta, Leo, Luciana M., Szczesniak, Anna-Maria, Hurst, Dow P., Schaffer, Peter C., Zagzoog, Ayat, Black, Tallan, Deschamps, Jeffrey R., Miess, Elke, Schulz, Stefan, Janero, David R., Straiker, Alex, Pertwee, Roger G., Abood, Mary E., Kelly, Melanie E. M., Reggio, Patricia H., Laprairie, Robert B., Thakur, Ganesh A.
Format:	Journal Article
Language:	English
Published:	WASHINGTON Amer Chemical Soc 24.06.2021
Subjects:	Allosteric Site Animals Cannabinoid Receptor Agonists - chemical synthesis Cannabinoid Receptor Agonists - metabolism Cannabinoid Receptor Agonists - therapeutic use Chemistry, Medicinal CHO Cells Cricetulus Glaucoma - drug therapy HEK293 Cells Hippocampus - cytology Humans Indoles - chemical synthesis Indoles - metabolism Indoles - therapeutic use Intraocular Pressure - drug effects Life Sciences & Biomedicine Ligands Male Mice Mice, Inbred C57BL Molecular Conformation Molecular Docking Simulation Molecular Dynamics Simulation Neurons - drug effects Pharmacology & Pharmacy Receptor, Cannabinoid, CB1 - agonists Receptor, Cannabinoid, CB1 - chemistry Receptor, Cannabinoid, CB1 - metabolism Science & Technology Stereoisomerism Structure-Activity Relationship CB1 DRUG DISCOVERY ENDOCANNABINOID SYSTEM PROTEIN-COUPLED RECEPTORS FUNCTIONAL SELECTIVITY GENERAL FORCE-FIELD INTRAOCULAR-PRESSURE BINDING MU-OPIOID RECEPTOR AGONIST
ISSN:	0022-2623, 1520-4804, 1520-4804
Online Access:	Get more information
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