Identification of NVP-TNKS656: The use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor

Journal of Medicinal Chemistry

Volumn 56, Issue 16, 2013, Pages 6495-6511

  Shultz, Michael D ^a   Cheung, Atwood K ^a   Kirby, Christina A ^a   Firestone, Brant ^a   Fan, Jianmei ^a   Chen, Christine Hiu Tung ^a   Chen, Zhouliang ^a   Chin, Donovan N ^a   Dipietro, Lucian ^a   Fazal, Aleem ^a   Feng, Yun ^a   Fortin, Pascal D ^a   Gould, Ty ^a   Lagu, Bharat ^a   Lei, Huangshu ^a   Lenoir, Francois ^a   Majumdar, Dyuti ^a   Ochala, Etienne ^a   Palermo, M G ^a   Pham, Ly ^a   Pu, Minying ^a   Smith, Troy ^a   Stams, Travis ^a   Tomlinson, Ronald C ^a   Touré, B Barry ^a   Visser, Michael ^a   Wang, Run Ming ^a   Waters, Nigel J ^a   Shao, Wenlin ^a   more..

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (4 BROMOPHENYL) 7,8 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 (4 CHLOROPHENYL) 7,8 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 (4 METHOXYPHENYL) 7,8 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 (AMINOMETHYL) 7,8 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 (AZIDOMETHYL) 7,8 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 (THIOPHEN 3 YL) 7,8 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 [4 (2 HYDROXYPROPAN 2 YL)PHENYL] 7,8 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 [4 (4 FLUOROBENZOYL)PIPERIDIN 1 YL] N [(4 OXO 4,5,7,8 TETRAHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 2 YL)METHYL] N (THIOPHEN 2 YLMETHYL)ACETAMIDE; 2 [4 (4 FLUOROBENZOYL)PIPERIDIN 1 YL] N [(4 OXO 4,5,7,8 TETRAHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 2 YL)METHYL]ACETAMIDE; 2 [4 (DIMETHYLAMINO)PHENYL] 7,8 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 [4 (METHYLSULFONYL)PHENYL] 7,8 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 [4 (TRIFLUOROMETHOXY)PHENYL] 7,8 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 [4 (TRIFLUOROMETHYL)PHENYL] 4A,5,7,7A TETRAHYDROTHIENO[3,4 D]PYRIMIDIN 4(3H) ONE; 2 [4 (TRIFLUOROMETHYL)PHENYL] 5,6 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(8H) ONE; 2 [4 (TRIFLUOROMETHYL)PHENYL] 5,6,7,8 TETRAHYDROQUINAZOLIN 4(3H) ONE; 2 [4 (TRIFLUOROMETHYL)PHENYL] 7,8 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 [4 (TRIFLUOROMETHYL)PHENYL] 7,8 DIHYDRO 3H THIOPYRANO[3,2 D]PYRIMIDIN 4(6H) ONE; 2 [4 (TRIFLUOROMETHYL)PHENYL] 7,8 DIHYDRO 3H THIOPYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 [4 (TRIFLUOROMETHYL)PHENYL]QUINAZOLIN 4(3H) ONE; 2 [[(THIOPHEN 2 YLMETHYL)AMINO]METHYL] 7,8 DIHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 4(5H) ONE; 2 CHLOROMETHYL 3,5,7,8 TETRAHYDROPYRANO[4,3 D]PYRIMIDIN 4 ONE; BETA CATENIN; GLYCOSYLTRANSFERASE INHIBITOR; N (CYCLOPROPYLMETHYL) 2 [4 (4 METHOXYBENZOYL)PIPERIDIN 1 YL) N [(4 OXO 4,5,7,8 TETRAHYDRO 3H PYRANO[4,3 D]PYRIMIDIN 2 YL)METHYL]ACETAMIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 2; NVPTNKS 656; PYRAN; TANKYRASE; UNCLASSIFIED DRUG; UNINDEXED DRUG; WNT PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; BREAST ADENOCARCINOMA; CHEMICAL MODIFICATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG ABSORPTION; DRUG BILE LEVEL; DRUG BINDING SITE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG CONJUGATION; DRUG DESIGN; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG GLUCURONIDATION; DRUG HALF LIFE; DRUG IDENTIFICATION; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG STABILITY; DRUG SYNTHESIS; ENTEROHEPATIC CIRCULATION; ENTHALPY; EXPERIMENTAL MODEL; FEMALE; ISOTHERMAL TITRATION CALORIMETRY; LIPOPHILICITY; LIVER MICROSOME METABOLISM; MAXIMUM PLASMA CONCENTRATION; MOUSE; MOUSE MAMMARY TUMOR ONCOVIRUS; NONHUMAN; PHARMACOPHORE; PROCESS OPTIMIZATION; RAT; STRUCTURE ACTIVITY RELATION; THERMODYNAMICS; TIME TO MAXIMUM PLASMA CONCENTRATION; TUMOR XENOGRAFT;

ACETAMIDES; ADMINISTRATION, ORAL; ANIMALS; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; ENZYME INHIBITORS; MICE; MODELS, MOLECULAR; PYRIMIDINONES; STRUCTURE-ACTIVITY RELATIONSHIP; TANKYRASES;

EID: 84883159741     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400807n     Document Type: Article

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