Conformational Restriction Leading to a Selective CB2 Cannabinoid Receptor Agonist Orally Active Against Colitis.
Basic Information
ID: ALA3421616
Journal: ACS Med Chem Lett
Title: Conformational Restriction Leading to a Selective CB2 Cannabinoid Receptor Agonist Orally Active Against Colitis.
Authors: El Bakali J, Muccioli GG, Body-Malapel M, Djouina M, Klupsch F, Ghinet A, Barczyk A, Renault N, Chavatte P, Desreumaux P, Lambert DM, Millet R.
Abstract: The CB2 cannabinoid receptor has been implicated in the regulation of intestinal inflammation. Following on from the promising activity of a series of 4-oxo-1,4-dihydroquinoline-3-carboxamide, we developed constrained analogues based on a 2H-pyrazolo[4,3-c]quinolin-3(5H)-one scaffold, with improved affinity for the hCB2 receptor and had very high selectivity over the hCB1 receptor. Importantly, the lead of this series (26, hCB2: K i = 0.39 nM, hCB1: K i > 3000 nM) was found to protect mice against experimental colitis after oral administration.
CiteXplore: 25699149
DOI: 10.1021/ml500439x
Patent ID: ┄