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- W2217045346 abstract "Non-steroidal anti-inflammatory drugs (NSAIDs) exert their pharmacological effects by inhibiting cyclooxygenase (COX)-1 and COX-2. Though widely prescribed for pain and inflammation, these agents have limited utility in chronic diseases due to serious mechanism-based adverse events such as gastrointestinal damage. Concomitant blockade of fatty acid amide hydrolase (FAAH) enhances the therapeutic effects of the NSAIDs while attenuating their propensity to cause gastrointestinal injury. This favorable interaction is attributed to the accumulation of protective FAAH substrates, such as the endocannabinoid anandamide, and suggests that agents simultaneously targeting COX and FAAH might provide an innovative strategy to combat pain and inflammation with reduced side effects. Here, we describe the rational design and structure-active relationship (SAR) properties of the first class of potent multitarget FAAH-COX inhibitors. A focused SAR exploration around the prototype 10r (ARN2508) led to the identification of achiral (18b) as well as racemic (29a-c and 29e) analogs. Absolute configurational assignment and pharmacological evaluation of single enantiomers of 10r are also presented. (S)-(+)-10r is the first highly potent and selective chiral inhibitor of FAAH-COX with marked in vivo activity, and represents a promising lead to discover novel analgesics and anti-inflammatory drugs." @default.
- W2217045346 created "2016-06-24" @default.
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- W2217045346 date "2016-02-01" @default.
- W2217045346 modified "2023-10-06" @default.
- W2217045346 title "Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies" @default.
- W2217045346 cites W105152574 @default.
- W2217045346 cites W1488365705 @default.
- W2217045346 cites W163232253 @default.
- W2217045346 cites W1898410235 @default.
- W2217045346 cites W1965657265 @default.
- W2217045346 cites W1970749696 @default.
- W2217045346 cites W1974097493 @default.
- W2217045346 cites W1975292133 @default.
- W2217045346 cites W1975313448 @default.
- W2217045346 cites W1975956160 @default.
- W2217045346 cites W1978417413 @default.
- W2217045346 cites W1979046480 @default.
- W2217045346 cites W1979963836 @default.
- W2217045346 cites W1980256331 @default.
- W2217045346 cites W1980990431 @default.
- W2217045346 cites W1982103270 @default.
- W2217045346 cites W1983113875 @default.
- W2217045346 cites W1986383551 @default.
- W2217045346 cites W1987775880 @default.
- W2217045346 cites W1990144502 @default.
- W2217045346 cites W1991262879 @default.
- W2217045346 cites W1997391943 @default.
- W2217045346 cites W1998465336 @default.
- W2217045346 cites W2004572576 @default.
- W2217045346 cites W2005308104 @default.
- W2217045346 cites W2005861756 @default.
- W2217045346 cites W2010311152 @default.
- W2217045346 cites W2010967782 @default.
- W2217045346 cites W2013381732 @default.
- W2217045346 cites W2016354440 @default.
- W2217045346 cites W2019144812 @default.
- W2217045346 cites W2022285221 @default.
- W2217045346 cites W2023167233 @default.
- W2217045346 cites W2024009660 @default.
- W2217045346 cites W2026469610 @default.
- W2217045346 cites W2029655841 @default.
- W2217045346 cites W2030850720 @default.
- W2217045346 cites W2036353767 @default.
- W2217045346 cites W2037723020 @default.
- W2217045346 cites W2053854129 @default.
- W2217045346 cites W2057893978 @default.
- W2217045346 cites W2060468714 @default.
- W2217045346 cites W2061046645 @default.
- W2217045346 cites W2065679828 @default.
- W2217045346 cites W2068426529 @default.
- W2217045346 cites W2072331499 @default.
- W2217045346 cites W2075072943 @default.
- W2217045346 cites W2077840364 @default.
- W2217045346 cites W2092787846 @default.
- W2217045346 cites W2103010344 @default.
- W2217045346 cites W2105771810 @default.
- W2217045346 cites W2108777528 @default.
- W2217045346 cites W2126408482 @default.
- W2217045346 cites W2129935236 @default.
- W2217045346 cites W2131051512 @default.
- W2217045346 cites W2135853706 @default.
- W2217045346 cites W2143684129 @default.
- W2217045346 cites W2145630011 @default.
- W2217045346 cites W2150586689 @default.
- W2217045346 cites W2155674292 @default.
- W2217045346 cites W2159963225 @default.
- W2217045346 cites W2163895651 @default.
- W2217045346 cites W2169886283 @default.
- W2217045346 cites W2171125004 @default.
- W2217045346 cites W2318298375 @default.
- W2217045346 cites W2415100273 @default.
- W2217045346 cites W4234676427 @default.
- W2217045346 cites W4241363254 @default.
- W2217045346 cites W4254752226 @default.
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- W2217045346 doi "https://doi.org/10.1016/j.ejmech.2015.12.036" @default.
- W2217045346 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4752335" @default.
- W2217045346 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26774927" @default.
- W2217045346 hasPublicationYear "2016" @default.
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