1,721,303 research outputs found
Monoglyceride lipase: Structure and inhibitors
Full text linkMonoglyceride lipase (MGL), the main enzyme responsible for the hydrolytic deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), is an intracellular serine hydrolase that plays critical roles in many physiological and pathological processes, such as pain, inflammation, neuroprotection and cancer. The crystal structures of MGL that are currently available provide valuable information about how this enzyme might function and interact with site-directed small-molecule inhibitors. On the other hand, its conformational equilibria and the contribution of regulatory cysteine residues present within the substrate-binding pocket or on protein surface remain open issues. Several classes of MGL inhibitors have been developed, from early reversible ones, such as URB602 and pristimerin, to carbamoylating agents that react with the catalytic serine, such as JZL184 and more recent O-hexafluoroisopropyl carbamates. Other inhibitors that modulate MGL activity by interacting with conserved regulatory cysteines act through mechanisms that deserve to be more thoroughly investigated
Fatty acid amide hydrolase inhibitors: a patent review (2009 - 2014)
Full text linkIntroduction: Fatty acid amide hydrolase (FAAH) is a key enzyme responsible for the degradation of the endocannabinoid anandamide. FAAH inactivation is emerging as a strategy to treat several CNS and peripheral diseases, including inflammation and pain. The search for effective FAAH inhibitors has thus become a key focus in present drug discovery.
Areas covered: Patents and patent applications published from 2009 to 2014 in which novel chemical classes are claimed to inhibit FAAH.
Expert opinion: FAAH is a promising target for treating many disease conditions including pain, inflammation and mood disorders. In the last few years, remarkable efforts have been made to develop new FAAH inhibitors (either reversible and irreversible) characterized by excellent potency and selectivity, to complete the arsenal of tools for modulating FAAH activity. The failure of PF-04457845 in a Phase II study on osteoarthritis pain has not flattened the interest in FAAH inhibitors. New clinical trials on ‘classical’ FAAH inhibitors are now ongoing, and new strategies based on compounds with peculiar in vivo distribution (e.g., peripheral) or with multiple pharmacological activities (e.g., FAAH and COX) are under investigation and could boost the therapeutic potential of this class in the next future
US20100311711 A1 - Inhibitors of NAAA and Methods Thereof
No full textCompounds and pharmaceutical compositions are contemplated that inhibit N-acyl-ethanolamine-hydrolyzing acid amidase (NAAA) to so increase the concentration of the substrate of NAAA, palmitoylethanolamine (PEA). NAAA inhibition is contemplated to be effective to alleviate conditions associated with a reduced concentration of PEA. Among other uses, various NAAA inhibitors are especially contemplated as therapeutic agents in the treatment of inflammatory diseases
Modulation of Anxiety Through Blockade of Anandamide Hydrolysis
No full textFatty acid amide hydrolase inhibitors of Formula I are provided. Pharmaceutical compositions comprising the compounds and methods of using them to inhibit FAAH and/or treat appetite disorder, glaucoma, pain, insomnia and neurological and psychological disorders including anxiety disorders, epilepsy and depression are provided
Chiral NMR discrimination of the diastereoisomeric salts of the H(3)-antagonist 2-[3-(1H-imidazol-4-ylmethyl)piperidin-1-yl]-1H-benzimidazole.
No full textDiastereomeric salts with optically pure (S)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetic acid (MTPA) were used to discriminate the enantiomers of the chiral H(3)-antagonist 2-[3-(1H-imidazol-4-ylmethyl)piperidin-1-yl]-1H-benzimidazole. Chemical-shift differences (Delta delta) in NMR spectra strongly depend on solvent and stoichiometric ratio. The better observable differentiation occurred for the proton at the 2-position of the imidazole ring
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