gem-Dimethyl-bearing C-Glucosides as Sodium-glucose Co-transporter 2 (SGLT2) Inhibitors.pdfVIP
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gem-Dimethyl-bearing C-Glucosides as Sodium-glucose Co-transporter 2 (SGLT2) Inhibitors.pdf
FULLPAPE
gem-Dimethyl-bearing GlucosidesasSodium—glucose
Co—transporter2(SGLT2)Inhibitors
Shi,Yongheng (史永恒) Zhao,Guilong (赵桂龙) Lou,Yuanyuan。(楼袁嫒)
Wang,Yuli(王玉丽) Shao,Hua。(邵华) Liu,Wei。(刘巍)
Xu,Weiren (徐为人) Tang,Lida,。(汤立达)
“SchoolofPharmacy,TianjinMedicalUniversity,Tianjin300070,China
“ KeyLaboratoryofMolecularDesignandDrugDiscovery,n “ Instituteo2
PharmaceuticalResearch, “ 300193,China
CollegeoJChemistryandMolecularEngineering,QingdaoUniversityofScienceand
Technology,Qingdao,Shandong266042,China
Threenovelgem—dimethylC—glucosidesweredesignedassodium—glucoseco—transporter2(SGLT2)inhibitors,
andtheirsynthesesstartedfrom D—-glucoseandthree2-substituted--5b··romobenzoicacidswereachievedviaafacile
8-stepprotocol,withthekeystepbeinganhydrousaluminum chloride—catalyzedFriedel—Craftsalkylationoftertiary
alcoholsandpheneto1.ThesethreeSGLT2inhibitorswereevaluated nvivowithamiceoralglucosetolerancetest
(OGTT),andtheanti—hyperglycemicactivitiesofallthesethreecompoundswerecomparablewiththatofthepositive
controiDapagliflozin.
Keywords sodium—glucoseco—transporter2 (SGLT2),gem—dimethyl,synthesis,Friedel—Craftsalkylation,oral
glucosetolerancetest(OGTT)
lntrOduCtiOn versusSGLT1and metabolically liable to 一glucose—
dase—mediatedcleavageinthesmallintestine.一Encour—
Patientswithtype2diabetessufferfrom hypergly—
aged by theobservationsofundin the investigation of
cem iathatisaconsequenceofimpaired insulin s
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