Identification of novel HSP90α/β isoform selective inhibitors using structure-based drug design. demonstration of potential utility in treating CNS disorders such as huntington's disease

Journal of Medicinal Chemistry

Volumn 57, Issue 8, 2014, Pages 3382-3400

  Ernst, Justin T ^a   Neubert, Timothy ^a   Liu, Michael ^a   Sperry, Samuel ^a   Zuccola, Harmon ^a   Turnbull, Amy ^a   Fleck, Beth ^a   Kargo, William ^a   Woody, Lisa ^a   Chiang, Peggy ^a   Tran, Dao ^a   Chen, Weichao ^a   Snyder, Phillip ^a   Alcacio, Timothy ^a   Nezami, Azin ^a   Reynolds, James ^a   Alvi, Khisal ^a   Goulet, Lance ^a   Stamos, Dean ^a  

^a VERTEX PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (2 CYCLOPROPYLETHYL) 4 (2,7,7 TRIMETHYL 5 OXO 3,4,5,6,7,8 HEXAHYDURO 1H PYRIDO[3,4 B]INDOL 9(2H) YL]BENZAMIDE; 2 [(TETRAHYDROFURAN 3 YL) 4 (2,7,7, TRIMETHYL 5 OXO 3,4,5,6,7,8 HEXAHYDRO 1H PYRIDO[3,4 B]INDOL 9(2H) YL]BENZAMIDE; 2,7,7 TRIMETHYL 9 (1 OXO 1,2,3,4 TETRAHYDROISOQUINOLIN 6 YL) 3,4,5,6,7,8,9 HEXAHYDRO 1H PYRIDO[3,4 B]INDOL 5(2H) ONE; 2,7,7 TRIMETHYL 9 (1 OXO 2,3,4,5 TETRAHYDRO 1H BENZO[C]AZEPIN 7 YL) 3,4,5,6,7,8,9 HEXAHYDRO 1H PYRIDO[3,4 B]INDOL 5(2H) ONE; 2,7,7 TRIMETHYL 9 (1 OXO ISOINDOLIN 5 YL) 3,4,5,6,7,8,9 HEXAHYDRO 1H PYRIDO[3,4 B]INDOL 5(2H) ONE; 3 [(4 CHLOROPYRIDIN 3 YL)AMINO] 5,5 DIMETHYLCYCLOHEX 2 ENONE; 4 (2,2 DIMETHYL 4 OXO 3,4,5,6,7,8 HEXAHYDRO 1H CARBAZOL 9(2H) 2 [(TETRAHYDROFURAN 3 YL)AMINO]BENZAMIDE; 8 (3 FLUOROPHENYL) 6 (3,6,6 TRIMETHYL 4 OXO 4,5,6,7 TETRAHYDRO 1H INDOL 1 YL) 3,4 DIHYDROISOQUINOLIN 1(2H) ONE; 8 (4 FLUOROPHENYL) 6 (3,6,6 TRIMETHYL 4 OXO 4,5,6,7 TETRAHYDRO 1H INDOL 1 YL) 3,4 DIHYDROISOQUINOLIN 1(2H) ONE; 8 (4 METHOXYPHENYL) 6 (3,6,6 TRIMETHYL 4 OXO 4,5,6,7 TETRAHYDRO 1H INDOL 1 YL) 3,4 DIHYDROISOQUINOLIN 1(2H) ONE; 8 (8 ISOBUTYL 1 OXO 1,2,3,4 TETRAHYDROISOQUINOLIN 6 YL) 2,7,7 TRIMETHYL 3,4,5,6,7,8,9 HEXAHYDRO 1H PYRIDO[3,4 B]INDOL 5(2H) ONE; 8 (TETRAHYDRO 2H PYRAN 4 YL) 6 (3,6,6 TRIMETHYL 4 OXO 4,5,6,7 TETRAHYDRO 1H INDOL 1 YL) 3,4 DIHYDROISOQUINOLIN 1(2H) ONE; 8 BENZYL 6 (3,6,6 TRIMETHYL 4 OXO 4,5,6,7 TETRAHYDRO 1H INDOL 1 YL) 3,4 DIHYDROISOQUINOLIN 1(2H) ONE; 8 BUTYL 6 (3,6,6 TRIMETHYL 4 OXO 4,5,6,7 TETRAHYDRO 1H INDOL 1 YL) 3,4 DIHYDROISOQUINOLIN 1(2H) ONE; 8 CYCLOBUTYL 6 (3,6,6 TRIMETHYL 4 OXO 4,5,6,7 TETRAHYDRO 1H INDOL 1 YL) 3,4 DIHYDROISOQUINOLIN 1(2H) ONE; 8 CYCLOHEXYL 6 (3,6,6 TRIMETHYL 4 OXO 4,5,6,7 TETRAHYDRO 1H INDOL 1 YL) 3,4 DIHYDROISOQUINOLIN 1(2H) ONE; 8 CYCLOPENTYL 6 (3,6,6 TRIMETHYL 4 OXO 4,5,6,7 TETRAHYDRO 1H INDOL 1 YL) 3,4 DIHYDROISOQUINOLIN 1(2H) ONE; 8 ISOBUTYL 6 (3,6,6 TRIMETHYL 4 OXO 4,5,6,7 TETRAHYDRO 1H INDOL 1 YL) 3,4 DIHYDROISOQUINOLIN 1(2H) ONE; 8 PHENYL 6 (3,6,6 TRIMETHYL 4 OXO 4,5,6,7 TETRAHYDRO 1H INDOL 1 YL) 3,4 DIHYDROISOQUINOLIN 1(2H) ONE; CARBOLINE DERIVATIVE; CYCLIC AMP DEPENDENT PROTEIN KINASE; GLUCOSE REGULATED PROTEIN 94; HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 90; HEAT SHOCK PROTEIN 90 INHIBITOR; HEAT SHOCK PROTEIN 90ALPHA; HEAT SHOCK PROTEIN 90BETA; HUNTINGTIN; INTERCELLULAR ADHESION MOLECULE 1; LACTAM; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; BLOOD BRAIN BARRIER; CALORIMETRY; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; CYCLIZATION; DRUG BINDING; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG HALF LIFE; DRUG SYNTHESIS; ENDOPLASMIC RETICULUM; FIBROBLAST; HUMAN; HUMAN CELL; HUNTINGTON CHOREA; HYDROGEN BOND; HYDROGENATION; HYDROLYSIS; IN VITRO STUDY; MALE; NONHUMAN; PLASMA CONCENTRATION-TIME CURVE; RAT; SINGLE DRUG DOSE; WESTERN BLOTTING;

ANIMALS; DRUG DESIGN; HSP90 HEAT-SHOCK PROTEINS; HUMANS; HUNTINGTON DISEASE; MALE; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84899578167     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500042s     Document Type: Article

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