Design and Synthesis of Novel Spiro Derivatives as Potent and Reversible Monoacylglycerol Lipase (MAGL) Inhibitors: Bioisosteric Transformation from 3-Oxo-3,4-dihydro-2<i>H</i>-benzo[<i>b</i>][1,4]oxazin-6-yl Moiety
Shuhei Ikeda, Hideyuki Sugiyama, Hidekazu Tokuhara, Masataka Murakami, Minoru Nakamura, Yuya Oguro, Jumpei Aida, Nao Morishita, Satoshi Sogabe, Douglas R. Dougan, Sean C. Gay, Ling Qin, Naoto Arimura, Yasuko Takahashi, Masako Sasaki, Yusuke Kamada, Kazunobu Aoyama, Kouya Kimoto, Makoto Kamata
Abstract
6.2 nM), good oral absorption, blood-brain barrier penetration, and significant pharmacodynamic changes (2-arachidonoylglycerol increase and arachidonic acid decrease) at 0.3-10 mg/kg, po. in mice.
Topics & Concepts
Monoacylglycerol lipaseChemistryMoietyStereochemistryIC50Combinatorial chemistryPharmacologyBiochemistryIn vitroReceptorEndocannabinoid systemMedicineCannabis and Cannabinoid ResearchPharmacological Receptor Mechanisms and EffectsNeurotransmitter Receptor Influence on Behavior