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

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

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