Synthesis of Triazole-Linked Amino Acid-Aryl C-Glycoside Hybrids via Click Chemistry as Novel PTPIB Inhibitors.pdfVIP
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Synthesis of Triazole-Linked Amino Acid-Aryl C-Glycoside Hybrids via Click Chemistry as Novel PTPIB Inhibitors.pdf
FULLPAPER
SynthesisofTriazole-L·inkedAminoAcid-A·rylC-Glycoside
HybridsviaClickChemistryasNovelPTP1B Inhibitors
Wang,Jia(汪佳) He,Xiaopeng(贺晓鹏) Gao,Lixin。(高立信) Sheng,Li。(盛利)
Shi,Xiaoxin(施小新) Li,Jia,。(李佳) Chen,Guorong。(陈国荣)
KeyLaboratoryforAdvancedMaterialsandInstituteofFineChemicals,andSchoolofPharmacy,EastChina
UniversityofScienceandTechnology,Shanghai200237,China
NationalCenterforDrugScreening,StateKeyLaboratoryofDrugResearch,ShanghaiInstituteofMateria
Medica,ShanghaiInstitutesofBiologicalSciences,ChineseAcademyofSciences,Shanghai201203,China
Triazolylphenylalanineandtyrosine-—arylC-glycosidehybridswerereadilysynthesizedviamicrowave-·assisted
Cu0)一catalyzedazide—alkyne1,3一dipolarcycloadditioninhighyields.Successiveenzymaticassayidentifiedthe
synthesizedglycoconjugatesasnovelPTP1Binhibitorswithlowmicromole—rangedinhibitoryactivityandatleast
several—foldselectivityoverotherhomologousPTPstested.Inaddition,thebenzylgroupsonglucosylmoietywere
foundcrucialtowedPTP1B inhibition.
Keywords clickchemistry,C—glycoside,triazolylaminoacid,PTP,inhibitors
Introduction metics.Hence,thedisclosureofnovelPTP1B inhibitor
entitiesremainsfairlydesirable.
Therehasbeenconsiderableinterestinthedevelop—
Carbohydratesubiquitously existin nature,which
mentofproteintyrosinephosphatase1B (PTP1B)in— govern numerouspivotalbiologicaland pathological
hibitorssincethisnegativesignalingenzymeisdirectly
events.Theuseofcarbohydratesasstart
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