Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6- dihydrobenzo[f]imidazo[1,2- d ][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2- methylpropanamide (GDC-0032): A β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity

Journal of Medicinal Chemistry

Volumn 56, Issue 11, 2013, Pages 4597-4610

  Ndubaku, Chudi O ^a   Heffron, Timothy P ^a   Staben, Steven T ^a   Baumgardner, Matthew ^a   Blaquiere, Nicole ^a   Bradley, Erin ^a   Bull, Richard ^b   Do, Steven ^a   Dotson, Jennafer ^a   Dudley, Danette ^a   Edgar, Kyle A ^a   Friedman, Lori S ^a   Goldsmith, Richard ^a   Heald, Robert A ^b   Kolesnikov, Aleksandr ^a   Lee, Leslie ^a   Lewis, Cristina ^a   Nannini, Michelle ^a   Nonomiya, Jim ^a   Pang, Jodie ^a   Price, Steve ^b   Prior, Wei Wei ^a,c   Salphati, Laurent ^a   Sideris, Steve ^a   Wallin, Jeffery J ^a   Wang, Lan ^a   Wei, Binqing ^a   Sampath, Deepak ^a   Olivero, Alan G ^a   more..

^a GENENTECH INC   (United States)

^b Argenta Discovery Ltd   (United Kingdom)

^c OncoMed Pharmaceuticals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 (TETRAHYDRO PYRAN 2 YLOXY) ETHYL] 4 (4,4,5,5 TETRAMETHYL [1,3,2]DIOXABOROLAN 2 YL 1H PYRAZOLE; 1 [4 [2 (2 ISOPROPYL 2H [1,2,4]TRIAZOL 3 YL) 4,5 DIHYDRO 6 OXA 1,3A DIAZA BENZO[E]AZULEN 8 YL] PYRAZOL 1 YL] 2 METHYL PROPAN 2 OL; 1 [4 [2 (2 ISOPROPYL 5 METHYL 2H [1,2,4]TRIAZOL 3 YL) 4,5 DIHYDRO 6 OXA 1,3A DIAZA BENZO[E]AZULEN 8 YL] PYRAZOL 1 YL] 2 METHYL PROPAN 2 OL; 2 (2 ISOPROPYL 5 METHYL 2H [1,2,4]TRIAZOL 3 YL) 8 (1 METHYL 1H PYRAZOL 4 YL) 4,5 DIHYDRO 6 OXA 1,3A DIAZA BENZO[E]AZULENE; 2 (4 (2 (2 ISOPROPYL 2H [1,2,4]TRIAZOL 3 YL) 4,5 DIHYDRO 6 OXA 3THIA 1 AZA BENZO[E]AZULEN 8 YL) PYRAZOL 1 YL) ETHANOL; 2 [3 [4 [2 (2 ISOPROPYL 5 METHYL 2H (1,2,4)TRIAZOL 3 YL) 4,5 DIHYDRO 6 OXA 1,3A DIAZA BENZO[E]AZULEN 8 YL] PYRAZOL 1 YL] AZETIDIN 1 YL] ETHANOL; 2 [4 [2 (2 ISOPROPYL 2H [1,2,4]TRIAZOL 3 YL) 4,5 DIHYDRO 6 OXA 1,3A DIAZA BENZO[E]AZULEN 8 YL] PYRAZOL 1 YL] ETHANOL; 2 [4 [2 (2 ISOPROPYL 5 METHYL 2H [1,2,4]TRIAZOL 3 YL) 4,5 DIHYDRO 6 OXA 1,3A DIAZA BENZO[E]AZULEN 8 YL PYRAZOL 1 YL] ETHANOL; 2 [4 [2 (2,5 METHYL 2H [1,2,4]TRIAZOL 3 YL) 4,5 DIHYDRO 6 OXA 1,3A DIAZA BENZO[E]AZULEN 8 YL] PYRAZOL 1 YL] ETHANOL; 2 [4 [2 (5 METHYL 2H [1,2,4]TRIAZOL 3 YL) 4,5 DIHYDRO 6 OXA 1,3A DIAZA BENZO[E]AZULEN 8 YL] PYRAZOL 1 YL] ETHANOL; 2 [4 [2 [2 (2,2,2 TRIFLUORO ETHYL) 2H [1,2,4]TRIAZOL 3 YL] 4,5 DIHYDRO 6 OXA 1,3A DIAZA BENZO[E]AZULEN 8 YL] PYRAZOL 1 YL] ETHANOL; 2 HYDROXY 1 [3 [4 [2 (2 ISOPROPYL 5 METHYL 2H [1,2,4]TRIAZOL 3 YL 4,5 DIHYDRO 6 OXA 1,3A DIAZA BENZO[E]AZULEN 8 YL] PYRAZOL 1 YL] AZETIDIN 1 YL] PROPAN 1 ONE; 2 METHYL 1 [4 (4,4,5,5 TETRAMETHYL [1,3,2]DIOXABOROLAN 2 YL) PYRAZOL 1 YL] PROPAN 2 OL; 4 (3 BROMOPHENOXY)BUTANOIC ACID; 4,8 DIBROMO 3,4 DIHYDROBENZO[B]OXEPIN 5(2H) ONE; 5 BROMO 2 (1H IMIDAZOL 2 YL)PHENOL; 8 BROMO 3,4 DIHYDROBENZO[B]OXEPIN 5(2H) ONE; 8 BROMO 4,5 DIHYDRO 6 OXA 3 THIA 1 AZA BENZO[E]AZULENE 2 CARBOXYLIC ACID; 8 BROMO 4,5 DIHYDRO 6 OXA 3 THIA 1 AZA BENZO[E]AZULENE 2 CARBOXYLIC ACID ETHYL ESTER; 9 BROMO 2 (1 (2,2,2 TRIFLUOROETHYL) 1H 1,2,4 TRIAZOL 5 YL) 5,6 DIHYDROBENZO[F ]IMIDAZOL[1,2 D][1,4]OXAZEPINE; 9 BROMO 2 (1 ISOPROPYL 1H 1,2,4 TRIAZOL 5 YL) 5,6 DIHYDROBENZO [F]IMIDAZO[1,2 D][1,4]OXAZEPINE; 9 BROMO 2 (1 ISOPROPYL 3 METHYL 1H 1,2,4 TRIAZOL 5 YL) 5,6 DIHYDROBENZO[F ]IMIDAZO[1,2 D][1,4]OXAZEPINE; 9 BROMO 2 IODO 5,6 DIHYDROBENZO[F ]IMIDAZO[1,2 D][1,4] OXAZEPINE; 9 BROMO 2,3 DIIODO 5,6 DIHYDROBENZO[F ]IMIDAZO[1,2 D][1,4] OXAZEPINE; 9 BROMO 5,6 DIHYDROBENZO[F ]IMIDAZO[1,2 D][1,4]OXAZEPINE; 9 BROMO 5,6 DIHYDROBENZO[F ]IMIDAZO[1,2 D][1,4]OXAZEPINE 2 CARBOXAMIDE; ANTINEOPLASTIC AGENT; ETHYL 4 (3 BROMOPHENOXY)BUTANOATE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; DRUG EXPOSURE; IN VIVO STUDY; NONHUMAN;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; DRUG SCREENING ASSAYS, ANTITUMOR; FEMALE; HEPATOCYTES; HUMANS; IMIDAZOLES; ISOENZYMES; MICE; MICE, NUDE; MICROSOMES, LIVER; NEOPLASM TRANSPLANTATION; OXAZEPINES; PHOSPHATIDYLINOSITOL 3-KINASE; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSPLANTATION, HETEROLOGOUS;

EID: 84879056371     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm4003632     Document Type: Article

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