α-Ketoheterocycle-Based Inhibitors of Fatty Acid Amide Hydrolase (FAAH)
نویسندگان
چکیده
منابع مشابه
Discovery and molecular basis of potent noncovalent inhibitors of fatty acid amide hydrolase (FAAH).
Fatty acid amide hydrolase (FAAH), an amidase-signature family member, is an integral membrane enzyme that degrades lipid amides including the endogenous cannabinoid anandamide and the sleep-inducing molecule oleamide. Both genetic knock out and pharmacological administration of FAAH inhibitors in rodent models result in analgesic, anxiolytic, and antiinflammatory phenotypes. Targeting FAAH act...
متن کاملN-aryl 2-aryloxyacetamides as a new class of fatty acid amide hydrolase (FAAH) inhibitors.
Fatty acid amide hydrolase (FAAH) is a promising target for the development of drugs to treat neurological diseases. In search of new FAAH inhibitors, we identified 2-(4-cyclohexylphenoxy)-N-(3-(oxazolo[4,5-b]pyridin-2-yl)phenyl)acetamide, 4g, with an IC50 of 2.6 µM as a chemical starting point for the development of potent FAAH inhibitors. Preliminary hit-to-lead optimisation resulted in 2-(4-...
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The pentane extract of the Peruvian plant Lepidium meyenii (Maca) has been shown to possess neuroprotective activity in vitro and in vivo. The involvement of the endocannabinoid system has been shown to be a possible mechanism of action. Some of the lipophilic constituents of Maca such as the macamides have been reported to possess significant pharmacological properties as shown in cell culture...
متن کاملExploration of a fundamental substituent effect of alpha-ketoheterocycle enzyme inhibitors: Potent and selective inhibitors of fatty acid amide hydrolase.
A series of C4 substituted alpha-ketooxazoles were examined as inhibitors of the serine hydrolase fatty acid amide hydrolase in efforts that further define and generalize a fundamental substituent effect on enzyme inhibitory potency. Thus, a plot of the Hammett sigma(m) versus -logK(i) provided a linear correlation (R(2)=0.90) with a slope of 3.37 (rho=3.37), that is of a magnitude that indicat...
متن کاملPotent and selective alpha-ketoheterocycle-based inhibitors of the anandamide and oleamide catabolizing enzyme, fatty acid amide hydrolase.
A study of the structure-activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed, targeting the 5-position of the oxazole. Examination of a series of substituted benzene derivatives (12-14) revealed that the optimal position for substitution was the meta-position with selected members approaching or exceeding the potency of 2f. Concurren...
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ژورنال
عنوان ژورنال: ACS Chemical Neuroscience
سال: 2012
ISSN: 1948-7193,1948-7193
DOI: 10.1021/cn2001206