Design, Synthesis and Evaluation of 6-Oxo-1, 6-dihydropyrimidine- 2,5-dicarboxamide Derivatives as MMP 13 Inhibitors研究.pdf

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Design, Synthesis and Evaluation of 6-Oxo-1, 6-dihydropyrimidine- 2,5-dicarboxamide Derivatives as MMP 13 Inhibitors研究.pdf

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Chem．Res．Chin．Univ．2013，29(1)，67—70 doi：10．1007／s40242-012-213l-2 Design，SynthesisandEvaluationof6-Oxo一1，6-dihydropyrimidine- 2,5-dicarboxamideDerivativesasMM P13Inhibitors LUHai．bin，WANGShi．han，LIQing．minandWANGYong．sheng，，．CollegeofPharmacy,JilinUniversity,Changchun130021．尸R．China, 2．ChangchunUniversityofChineseMedicine，Changchun130021， R．China Abstract Wedesignedandsynthsizedaseriesofnovel6-oxo-1，6-dihydropyrimidine一2，5-dicarboxamidederivatives andevaluatedtheirinhibitioneffectsonMMP3，MMP12na dMMP 13．Thepharmacologicalresultsshow thatthey havepotentandhighlyselectiveactivityofinhibitingMMP13． Keywords Matrixmetal1oproteinase13(MMPl3)；Matrixmetalloproteinase(MMP)；Inhibition 1 lntrOductiOn inhibitorsofMⅣIP13． The synthetic M ⅣlPs inhibitors with low moleculra Matrix metalloproteinases(MMPs) are a family of weightsareusedinthetreatmentofthesediseases．Theseinhi- Zn．dependentendOpeptidasesinvolvedinthedegradationna d bitorsgenerallyincludeazincbindinggroup(ZBG)，capableto repairofthemajorcomponentsoftheextracellularmatrixof efficientlychelatethecatalyticzincion．boundtoasubstrate- connective tissuest1,2J ． These enzymesare involved in many likefragmentdesignedtofittheS1primaryspecificitysubsite physiologicalprocesses such as ovulation，embryogenesis， nadadjacentsubsitesL“J．Hydroxamateisconsideredtobethe angiogenesis．cellulra differentiation，nadwound healingt3,4J． mostef