89667-15-2Relevant articles and documents
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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Paragraph 00398, (2013/10/08)
Provided herein are carbamate compounds which may be useful in the treatment of, for example, pain, solid tumors and/or obesity.
Effective lithiation of 3-bromopyridine: Synthesis of 3-pyridine boronic acid and variously 3-substituted pyridines
Cai, Dongwei,Larsen, Robert D,Reider, Paul J
, p. 4285 - 4287 (2007/10/03)
By using toluene as a solvent, 3-lithiopyridine can be generated cleanly at -50°C. The addition of various electrophiles affords useful building blocks, such as the 3-pyridine boronic acid in 87% isolated yield.
