{"data":{"id":"10.6084/m9.figshare.c.2131475.v1","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2131475.v1","prefix":"10.6084","suffix":"m9.figshare.c.2131475.v1","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Sundermann, Tom","nameType":"Personal","givenName":"Tom","familyName":"Sundermann","affiliation":[],"nameIdentifiers":[]},{"name":"Hanekamp, Walburga","nameType":"Personal","givenName":"Walburga","familyName":"Hanekamp","affiliation":[],"nameIdentifiers":[]},{"name":"Lehr, Matthias","nameType":"Personal","givenName":"Matthias","familyName":"Lehr","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Structure–activity relationship studies on 1-heteroaryl-3-phenoxypropan-2-ones acting as inhibitors of cytosolic phospholipase A\u003csub\u003e2\u003c/sub\u003e\u003cb\u003eα\u003c/b\u003e and fatty acid amide hydrolase: replacement of the activated ketone group by other serine traps"}],"publisher":"Figshare","container":{},"publicationYear":2015,"subjects":[{"subject":"Biophysics"},{"subject":"Biochemistry"},{"subject":"Microbiology"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Biological sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Neuroscience"},{"subject":"Pharmacology"},{"subject":"39999 Chemical Sciences not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Chemical sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Chemical sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Clinical medicine","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Hematology"}],"contributors":[],"dates":[{"date":"2015-12-05","dateType":"Created"},{"date":"2016-04-27","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"CC-BY","rightsUri":"http://creativecommons.org/licenses/by/3.0/us"}],"descriptions":[{"description":"Cytosolic phospholipase A\u003csub\u003e2\u003c/sub\u003eα (cPLA\u003csub\u003e2\u003c/sub\u003eα) and fatty acid amide hydrolase (FAAH) are serine hydrolases. cPLA\u003csub\u003e2\u003c/sub\u003eα is involved in the generation of pro-inflammatory lipid mediators, FAAH terminates the anti-inflammatory effects of endocannabinoids. Therefore, inhibitors of these enzymes may represent new drug candidates for the treatment of inflammation. We have reported that certain 1-heteroarylpropan-2-ones are potent inhibitors of cPLA\u003csub\u003e2\u003c/sub\u003eα and FAAH. The serine reactive ketone group of these compounds, which is crucial for enzyme inhibition, is readily metabolized resulting in inactive alcohol derivatives. In order to obtain metabolically more stable inhibitors, we replaced this moiety by α-ketoheterocyle, cyanamide and nitrile serine traps. Investigations on activity and metabolic stability of these substances revealed that in all cases an increased metabolic stability was accompanied by a loss of inhibitory potency against cPLA\u003csub\u003e2\u003c/sub\u003eα and FAAH, respectively.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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