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ID: ALA3400077

Journal: Bioorg Med Chem Lett

Title: Loratadine analogues as MAGL inhibitors.

Authors: Patel JZ, Ahenkorah S, Vaara M, Staszewski M, Adams Y, Laitinen T, Navia-Paldanius D, Parkkari T, Savinainen JR, Walczyński K, Laitinen JT, Nevalainen TJ.

Abstract: Compound 12a (JZP-361) acted as a potent and reversible inhibitor of human recombinant MAGL (hMAGL, IC50=46 nM), and was found to have almost 150-fold higher selectivity over human recombinant fatty acid amide hydrolase (hFAAH, IC50=7.24 μM) and 35-fold higher selectivity over human α/β-hydrolase-6 (hABHD6, IC50=1.79 μM). Additionally, compound 12a retained H1 antagonistic affinity (pA2=6.81) but did not show cannabinoid receptor activity, when tested at concentrations ⩽ 10 μM. Hence, compound 12a represents a novel dual-acting pharmacological tool possessing both MAGL-inhibitory and antihistaminergic activities.

CiteXplore: 25752982

DOI: 10.1016/j.bmcl.2015.02.037