2. Academic Validation
  3. Loratadine analogues as MAGL inhibitors

Loratadine analogues as MAGL inhibitors

  • Bioorg Med Chem Lett. 2015 Apr 1;25(7):1436-42. doi: 10.1016/j.bmcl.2015.02.037.
Jayendra Z Patel 1,  Stephen Ahenkorah 2,  Miia Vaara 3,  Marek Staszewski 4,  Yahaya Adams 2,  Tuomo Laitinen 2,  Dina Navia-Paldanius 3,  Teija Parkkari 2,  Juha R Savinainen 3,  Krzysztof Walczyński 4,  Jarmo T Laitinen 3,  Tapio J Nevalainen 2
Affiliations

Affiliations

  • 1 School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, PO Box 1627, FIN-70211 Kuopio, Finland. Electronic address: [email protected].
  • 2 School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, PO Box 1627, FIN-70211 Kuopio, Finland.
  • 3 School of Medicine, Institute of Biomedicine/Physiology, University of Eastern Finland, PO Box 1627, FIN-70211 Kuopio, Finland.
  • 4 Department of Synthesis and Technology of Drugs, Faculty of Pharmacy, Medical University of Lodz, 90-151 Lodz, Poland.
PMID: 25752982 DOI: 10.1016/j.bmcl.2015.02.037
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.

Keywords

2-Arachidonoyl glycerol; Fatty acid amide hydrolase; Loratadine; Monoacylglycerol lipase; α/β hydrolase-6.

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