224178-67-0Relevant articles and documents
Identification and optimization of soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase
Kodani, Sean D.,Bhakta, Saavan,Hwang, Sung Hee,Pakhomova, Svetlana,Newcomer, Marcia E.,Morisseau, Christophe,Hammock, Bruce D.
supporting information, p. 762 - 768 (2018/01/27)
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 herein initially started with t-TUCB (trans-4-[4-(3-trifluoromethoxyphenyl-l-ureido)-cyclohexyloxy]-benzoic acid), a potent sEH inhibitor that was previously shown to weakly inhibit FAAH. Inhibitors with a 6-fold increase of FAAH potency while maintaining high sEH potency were developed by optimization. Interestingly, compared to most FAAH inhibitors that inhibit through time-dependent covalent modification, t-TUCB and related compounds appear to inhibit FAAH through a time-independent, competitive mechanism. These inhibitors are selective for FAAH over other serine hydrolases. In addition, FAAH inhibition by t-TUCB appears to be higher in human FAAH over other species; however, the new dual sEH/FAAH inhibitors have improved cross-species potency. These dual inhibitors may be useful for future studies in understanding the therapeutic application of dual sEH/FAAH inhibition.
INHIBITORS FOR SOLUBLE EPOXIDE HYDROLASE (SEH) AND FATTY ACID AMIDE HYDROLASE (FAAH)
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Paragraph 0143, (2017/10/11)
The present invention provides compounds that are dual inhibitors of soluble epoxide hydrolase and fatty acid amide hydrolase. The present invention also provides methods of using the compounds to inhibit soluble epoxide hydrolase and fatty acid amide hydrolase, and to treat cancer.
NOVEL COMPOUNDS AS HISTAMINE H3 RECEPTOR LIGANDS
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Page/Page column 11, (2012/09/11)
The present invention relates to novel compounds of formula (I), and their pharmaceutically acceptable salts and compositions containing them. The present invention also relates to a process for the preparation of above said novel compounds, and their pha