Discovery of pyrazole as C-terminus of selective BACE1 inhibitors

European Journal of Medicinal Chemistry

Volumn 68, Issue , 2013, Pages 270-283

  Li, Jia ^b   Zou, Yiquan ^a   Xu, Lei ^b   Chen, Wuyan ^a   Zhu, Yiping ^a   Chen, Tiantian ^a   Fu, Yan ^a   Li, Li ^a   Ma, Lanping ^a   Xiong, Bing ^a   Wang, Xin ^a   Li, Jian ^a   He, Jianhua ^c   Zhang, Haiyan ^a   Xu, Yechun ^a   Shen, Jingkang ^a  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^b National Center for Drug Screening   (China)

^c SHANGHAI INSTITUTE OF APPLIED PHYSICS   (China)

Author keywords

Alzheimer's disease; BACE1; C terminus; Click chemistry; In situ screening assay; Pyrazole

Indexed keywords

BETA SECRETASE 1; BETA SECRETASE INHIBITOR; ETHYL 1 [3 [3 [1 (4 FLUOROPHENYL)ETHYLCARBAMOYL] 5 (N METHYLMETHYLSULFONAMIDO)BENZAMIDO] 2 HYDROXY 4 PHENYLBUTYL) 1H PYRAZOLE 4 CARBOXYLATE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 1 PHENYL 4 (1H 1,2,4 TRIAZOL 1 YL)BUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 1 PHENYL 4 (1H PYRAZOL 1 YL)BUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 1 PHENYL 4 (1H TETRAZO 1 YL)BUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 1 PHENYL 4 (2H TETRAZOL 2 YL)BUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 1 PHENYL 4 (4 PHENYL 1H 1,2,3 TRIAZOL 1 YL)BUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 1 PHENYL 4 (5 PHENYL 1H 1,2,3 TRIAZOL 1 YL)BUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 1 PHENYL 4 [4 (PIPERIDINE 1 CARBONYL) 1H PYRAZOL 1 YL]BUTAN 2 YL] 5 (N METHLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 1 PHENYL 4 [4 (PYRROLIDINE 1 CARBONYL) 1H PYRAZOL 1 YL]BUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 4 (1H IMIDAZOL 1 YL) 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 4 [4 (1 HYDROXY ETHYL) 1H 1,2,3 TRIAZOL 1 YL] 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 4 [4 (4 METHOXYPHENYL) 1H 1,2,3 TRIZOL 1 YL] 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 4 [4 (HYDROXYL METHYL) 1H PYRAZOL 1 YL] 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 4 [4 (METHYL CARBAMOYL) 1H PYRAZOL 1 YL] 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 4 [4 (MORPHOLINE 4 CARBONYL) 1H PYRAZOL 1 YL] 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3 [3 HYDROXY 4 [5 (HYDROXYMETHYL) 1H 1,2,3 TRIZOL 1 YL] 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3(3 HYDROXY 1 PHENYL 4 (1H 1,2,3 TRIAZOL 1 YL)BUTAN 2 YL) 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [1 (4 FLUOROPHENYL)ETHYL]N3[3 HYDROXY 4 [4 (HYDROXYLMETHYL) 1H 1,2,3 TRIAZOL 1 YL] 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [4 (4 CARBAMOYL 1H PYRAZOL 1 YL) 3 HYDROXY 1 PHENYLBUTAN 2 YL]N3 [1 (4 FLUOROPHENYL)ETHYL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [4 (4 CYCLOHEXYL 1H 1,2,3 TRIAZOL 1 YL) 3 HYDROXY 1 PHENYLBUTAN 2 YL]N3 [1 (4 FLUOROPHENYL)ETHYL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [4 [4 (AZEPANE 1 CARBONYL) 1H PYRAZOL 1 YL] 3 HYDROXY 1 PHENYLBUTAN 2 YL]N3 [1 (4 FLUOROPHENYL)ETHYL] 5 (N METHLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [4 [4 (DIETHYLCARBAMOYL) 1H PYRAZOL 1 YL]N3 HYDROXY 1 PHENYLBUTAN 2 YL]N3 [1 (4 FLUOROPHENYL)ETHYL] 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N1 [4 [4 (DIMETHYLCARBAMOYL) 1H PYRAZOL 1 YL] 3 HYDROXY 1 PHENYLBUTAN 2 YL]N3 [1 (4 FLUOROPHENYL)EHTYL] 5 (METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CLICK CHEMISTRY; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; STRUCTURE ACTIVITY RELATION;

ALZHEIMER'S DISEASE; BACE1; C-TERMINUS; CLICK CHEMISTRY; DCM; DICHLOROMETHANE; DIPEA; DMF; EDCL; ETHYL ACETATE; ETOAC; HOBT; IN SITU SCREENING ASSAY; N,N-DIISOPROPYLETHYLAMINE; N,N-DIMETHYLFORMAMIDE; N-(3-DIMETHYLAMINOPROPYL)-N′-ETHYLCARBODIIMIDE HYDROCHLORIDE; N-HYDROXYBENZOTRIAZOLE; PYRAZOLE; TETRAHYDROFURAN; THF;

AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ACID ENDOPEPTIDASES; CELLS, CULTURED; CRYSTALLOGRAPHY, X-RAY; DRUG DISCOVERY; ENZYME ACTIVATION; HUMANS; INHIBITORY CONCENTRATION 50; MICE; MICE, TRANSGENIC; PROTEASE INHIBITORS; PYRAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84883095375     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2013.06.027     Document Type: Article

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