Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2

Journal of Medicinal Chemistry

Volumn 57, Issue 15, 2014, Pages 6668-6678

  Clark, Michael P ^a   Ledeboer, Mark W ^a   Davies, Ioana ^a   Byrn, Randal A ^a   Jones, Steven M ^a   Perola, Emanuele ^a   Tsai, Alice ^a   Jacobs, Marc ^a   Nti Addae, Kwame ^a   Bandarage, Upul K ^a   Boyd, Michael J ^a   Bethiel, Randy S ^a   Court, John J ^a   Deng, Hongbo ^a   Duffy, John P ^a   Dorsch, Warren A ^a   Farmer, Luc J ^a   Gao, Huai ^a   Gu, Wenxin ^a   Jackson, Katrina ^a   Jacobs, Dylan H ^a   Kennedy, Joseph M ^a   Ledford, Brian ^a   Liang, Jianglin ^a   Maltais, François ^a   Murcko, Mark ^a   Wang, Tiansheng ^a   Wannamaker, M Woods ^a   Bennett, Hamilton B ^a   Leeman, Joshua R ^a   McNeil, Colleen ^a   Taylor, William P ^a   Memmott, Christine ^a   Jiang, Min ^a   Rijnbrand, Rene ^a   Bral, Christopher ^b   Germann, Ursula ^a   Nezami, Azin ^a   Zhang, Yuegang ^a   Salituro, Francesco G ^c   Bennani, Youssef L ^a   Charifson, Paul S ^a   more..

^a VERTEX PHARMACEUTICALS   (United States)

^b Arrowhead Research Corporation   (United States)

^c Sage Therapeutics Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (5 CHLORO 1 TOSYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 5 FLUORO N (PIPERIDIN 3 YL)PYRIMIDIN 4 AMINE; 3 (METHOXYCARBONYL)BICYCLO[2.2.2]OCT 5 ENE 2 CARBOXYLIC ACID; 3 [3 [[2 (5 CHLORO 1 TOSYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 5 FLUOROPYRIMIDIN 4 YL]AMINO]PIPERIDIN 1 YL]PROPANE 1,2 DIOL; 3 [3 [[2 (5 CHLORO 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 5 FLUOROPYRIMIDIN 4 YL]AMINO]PIPERIDIN 1 YL] PROPANE 1,2 DIOL; 3 [[5 FLUORO 2 (5 FLUORO 1H PYRROLO[2,3 B]PYRIDIN 3 YL)PYRIMIDIN 4 YL]AMINO]BICYCLO[2.2.2]OCTANE 2 CARBOXYLIC ACID; 4 ACETAMIDO 5 AMINO 3 (1 ETHYLPROPOXY) 1 CYCLOHEXENE 1 CARBOXYLIC ACID; 5 CHLORO 3 (4,4,5,5 TETRAMETHYL 1,3,2 DIOXABOROLAN 2 YL) 1 TOSYL 1H PYRROLO[2,3 B]PYRIDINE; 5 CHLORO 3 [5 FLUORO 4 (METHYLSULFINYL)PYRIMIDIN 2 YL] 1 TOSYL 1H PYRROLO[2,3 B]PYRIDINE; 5 CHLORO 3 [5 FLUORO 4 (METHYLTHIO)PYRIMIDIN 2 YL] 1 TOSYL 1H PYRROLO[2,3 B]PYRIDINE; ANTIVIRUS AGENT; CARBOXYLIC ACID DERIVATIVE; INDOLE DERIVATIVE; MESO ENDO TETRAHYDRO 4,7 ETHANOISOBENZOFURAN 1,3 DIONE; METHYL 3 AMINOBICYCLO[2.2.2]OCTANE 2 CARBOXYLATE; METHYL 3 [(2 CHLORO 5 FLUOROPYRIMIDIN 4 YL)AMINO]BICYCLO [2.2.2]OCTANE 2 CARBOXYLATE; METHYL 3 [[(BENZOLOXY)CARBONYL]AMINO] BICYCLO[2.2.2]OCT 5 ENE 2 CARBOXYLATE; METHYL 3 [[5 FLUORO 2 (5 FLUORO 1 TOSYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL)PYRIMIDIN 4 YL]AMINO]BICYCLO[2.2.2]OCTANE 2 CARBOXYLATE; METHYL 3 [[5 FLUORO 2 (5 FLUORO 1H PYRROLO[2,3 B] PYRIDIN 3 YL)PYRIMIDIN 4 YL]AMINO]BICYCLO[2.2.2]OCTANE 2 CARBOXYLATE; UNCLASSIFIED DRUG; VX 787; HETEROCYCLIC COMPOUND; PB2 PROTEIN, INFLUENZAVIRUS A; RNA DIRECTED RNA POLYMERASE; VIRUS PROTEIN;

2009 H1N1 INFLUENZA; ALKYLATION; ANIMAL CELL; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BINDING ASSAY; BINDING SITE; CELL ASSAY; CELL PROTECTION; CELL PROTECTION ASSAY; CONTROLLED STUDY; CRYSTAL STRUCTURE; CURTIUS REARRANGEMENT; CYCLOADDITION; DERIVATIZATION; DIELS ALDER REACTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG EFFICACY; DRUG SYNTHESIS; ENZYME BINDING; HEALTH CARE QUALITY; HYDROGEN BOND; HYDROGENATION; IN VITRO STUDY; INFLUENZA VIRUS A H5N1; LIPOPHILICITY; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; OXIDATION; POLARIZATION; RACEMIC MIXTURE; RAT; STEREOCHEMISTRY; STEREOISOMERISM; SUZUKI REACTION; WEIGHT REDUCTION; ANIMAL; ANTAGONISTS AND INHIBITORS; ANTIVIRAL RESISTANCE; BAGG ALBINO MOUSE; BIOAVAILABILITY; CHEMICAL STRUCTURE; CHEMISTRY; DOG; DRUG EFFECTS; INFLUENZA VIRUS A; MDCK CELL LINE; ORAL DRUG ADMINISTRATION; ORTHOMYXOVIRIDAE INFECTIONS; PHYSIOLOGY; SPECIES DIFFERENCE; STRUCTURE ACTIVITY RELATION; SYNTHESIS; VIRUS REPLICATION;

ADMINISTRATION, ORAL; ANIMALS; ANTIVIRAL AGENTS; AZA COMPOUNDS; BIOLOGICAL AVAILABILITY; DOGS; DRUG RESISTANCE, VIRAL; INDOLES; INFLUENZA A VIRUS; MADIN DARBY CANINE KIDNEY CELLS; MALE; MICE, INBRED BALB C; MODELS, MOLECULAR; MOLECULAR STRUCTURE; ORTHOMYXOVIRIDAE INFECTIONS; RATS; RNA REPLICASE; SPECIES SPECIFICITY; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; VIRAL PROTEINS; VIRUS REPLICATION;

EID: 84906089131     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm5007275     Document Type: Article

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