1446818-91-2Relevant academic research and scientific papers
Identification of ABX-1431, a Selective Inhibitor of Monoacylglycerol Lipase and Clinical Candidate for Treatment of Neurological Disorders
Cisar, Justin S.,Weber, Olivia D.,Clapper, Jason R.,Blankman, Jacqueline L.,Henry, Cassandra L.,Simon, Gabriel M.,Alexander, Jessica P.,Jones, Todd K.,Ezekowitz, R. Alan B.,O'Neill, Gary P.,Grice, Cheryl A.
, p. 9062 - 9084 (2018/09/06)
The serine hydrolase monoacylglycerol lipase (MGLL) converts the endogenous cannabinoid receptor agonist 2-arachidonoylglycerol (2-AG) and other monoacylglycerols into fatty acids and glycerol. Genetic or pharmacological inactivation of MGLL leads to elevation in 2-AG in the central nervous system and corresponding reductions in arachidonic acid and eicosanoids, producing antinociceptive, anxiolytic, and antineuroinflammatory effects without inducing the full spectrum of psychoactive effects of direct cannabinoid receptor agonists. Here, we report the optimization of hexafluoroisopropyl carbamate-based irreversible inhibitors of MGLL, culminating in a highly potent, selective, and orally available, CNS-penetrant MGLL inhibitor, 28 (ABX-1431). Activity-based protein profiling experiments verify the exquisite selectivity of 28 for MGLL versus other members of the serine hydrolase class. In vivo, 28 inhibits MGLL activity in rodent brain (ED50 = 0.5-1.4 mg/kg), increases brain 2-AG concentrations, and suppresses pain behavior in the rat formalin pain model. ABX-1431 (28) is currently under evaluation in human clinical trials.
CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME
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, (2013/07/19)
This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compunds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition.
CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME
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, (2013/10/08)
Provided herein are carbamate compounds which may be useful in the treatment of, for example, pain, solid tumors and/or obesity.
