A Second Generation of Carbamate-Based Fatty Acid Amide Hydrolase Inhibitors with Improved Activity in vivo
نویسندگان
چکیده
منابع مشابه
Mapping human brain fatty acid amide hydrolase activity with PET.
Endocannabinoid tone has recently been implicated in a number of prevalent neuropsychiatric conditions. [(11)C]CURB is the first available positron emission tomography (PET) radiotracer for imaging fatty acid amide hydrolase (FAAH), the enzyme which metabolizes the prominent endocannabinoid anandamide. Here, we sought to determine the most suitable kinetic modeling approach for quantifying [(11...
متن کاملIdentification and optimization of soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase.
Multi-target inhibitors have become increasing popular as a means to leverage the advantages of poly-pharmacology while simplifying drug delivery. Here, we describe dual inhibitors for soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH), two targets known to synergize when treating inflammatory and neuropathic pain. The structure activity relationship (SAR) study described her...
متن کاملStructure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase.
A systematic study of the structure-activity relationships of 2b (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1-napthyl, Ki = 2.6 nM), with 5hh (aryl = 3-ClPh, Ki = 900 pM) being 5-fold more potent than 2b...
متن کاملEx vivo imaging of fatty acid amide hydrolase activity and its inhibition in the mouse brain.
There is recent behavioral evidence that fatty acid amide hydrolase (FAAH) inhibitors produce a subset of cannabinoid receptor agonist effects, suggesting both anandamide-specific behavioral functions and possible regional differences in FAAH inhibitory effects. Here, we introduce a novel imaging method to quantify regional differences in brain FAAH activity. Upon intravenous [3H]anandamide adm...
متن کاملLuciferin Amides Enable in Vivo Bioluminescence Detection of Endogenous Fatty Acid Amide Hydrolase Activity
Firefly luciferase is homologous to fatty acyl-CoA synthetases. We hypothesized that the firefly luciferase substrate d-luciferin and its analogs are fatty acid mimics that are ideally suited to probe the chemistry of enzymes that release fatty acid products. Here, we synthesized luciferin amides and found that these molecules are hydrolyzed to substrates for firefly luciferase by the enzyme fa...
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ژورنال
عنوان ژورنال: ChemMedChem
سال: 2009
ISSN: 1860-7179,1860-7187
DOI: 10.1002/cmdc.200900210