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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2010-3-4
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pubmed:abstractText |
Fatty acid amide hydrolase (FAAH) is the key hydrolytic enzyme for the endogenous cannabinoid receptor ligand anandamide. The synthesis and evaluation for their FAAH inhibitory activities of a series of 18 paracetamol esters are described. Structure-activity relationship studies indicated that the ester (33) with a 2-(4-(2-(trifluoromethyl)pyridin-4-ylamino)phenyl)acetic acid substituent was the most potent analogue in this series. The compound inhibited FAAH activity in a competitive manner with a K(i) value of 0.16 microM. The compound was also able to inhibit the FAAH activity in rat basophilic leukemia cells as assessed by measuring either the hydrolysis of anandamide, the FAAH-dependent cellular accumulation of anandamide, or the FAAH-dependent recycling of tritium to the cell membranes. The compound also inhibited the activity of monoacylglycerol lipase (MGL), the enzyme responsible for the hydrolysis of the endogenous cannabinoid receptor ligand 2-arachidonoylglycerol, with an IC(50) value of 1.9 microM. It is concluded that the compound may be a useful template for the design of potent novel inhibitors of FAAH.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1520-4804
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
11
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2286-98
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pubmed:meshHeading |
pubmed-meshheading:20143779-Amidohydrolases,
pubmed-meshheading:20143779-Analgesics,
pubmed-meshheading:20143779-Animals,
pubmed-meshheading:20143779-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:20143779-Arachidonic Acids,
pubmed-meshheading:20143779-Benzoates,
pubmed-meshheading:20143779-Cell Line, Tumor,
pubmed-meshheading:20143779-Dose-Response Relationship, Drug,
pubmed-meshheading:20143779-Enzyme Inhibitors,
pubmed-meshheading:20143779-Inhibitory Concentration 50,
pubmed-meshheading:20143779-Kinetics,
pubmed-meshheading:20143779-Magnetic Resonance Spectroscopy,
pubmed-meshheading:20143779-Polyunsaturated Alkamides,
pubmed-meshheading:20143779-Pyridines,
pubmed-meshheading:20143779-Rats,
pubmed-meshheading:20143779-Rats, Sprague-Dawley,
pubmed-meshheading:20143779-Rats, Wistar,
pubmed-meshheading:20143779-Spectrophotometry, Infrared,
pubmed-meshheading:20143779-Structure-Activity Relationship
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pubmed:year |
2010
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pubmed:articleTitle |
Synthesis and evaluation of paracetamol esters as novel fatty acid amide hydrolase inhibitors.
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pubmed:affiliation |
Department of Toxicology, Unit of Medicinal Chemistry, University of Cagliari, via Ospedale 72, Cagliari I-09124, Italy. vonnis@unica.it
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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