Rational design of phosphoinositide 3-kinase inhibitors that exhibit selectivity over the phosphoinositide 3-kinase isoform

Journal of Medicinal Chemistry

Volumn 54, Issue 22, 2011, Pages 7815-7833

  Heffron, Timothy P ^a   Wei, Binqing ^a   Olivero, Alan ^a   Staben, Steven T ^a   Tsui, Vickie ^a   Do, Steven ^a   Dotson, Jennafer ^a   Folkes, Adrian J ^b   Goldsmith, Paul ^b   Goldsmith, Richard ^a   Gunzner, Janet ^a   Lesnick, John ^a   Lewis, Cristina ^a   Mathieu, Simon ^a   Nonomiya, Jim ^a   Shuttleworth, Stephen ^b   Sutherlin, Daniel P ^a   Wan, Nan Chi ^b   Wang, Shumei ^a   Wiesmann, Christian ^a   Zhu, Bing Yan ^a   more..

^a GENENTECH INC   (United States)

^b Piramed Pharma   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 (1H INDAZOL 4 YL) 6 (( 4 (METHYLSULFONYL)PIPERAZIN 1 YL)METHYL) 4 MORPHOLINOFURO[ 2,3 D]PYRIMIDINE; 4 ( 2 (1H INDAZOL 4 YL) 6 (( 4 (METHYLSULFONYL)PIPERAZIN 1 YL)METHYL)THIENO[ 2,3 D]PYRIMIDIN 4 YL)MORPHOLINE; 4 ( 2 (1H INDAZOL 4 YL)THIENO[ 2,3 D]PYRIMIDIN 4 YL)MORPHOLINE; 4 (( 2 ( 2 AMINOPYRIMIDIN 5 YL) 4 MORPHOLINOTHIENO[ 2,3 D]PYRIMIDIN 6 YL)METHYL) N,N DIMETHYLPIPERAZINE 1 CARBOXAMIDE; 5 ( 4 MORPHOLINO 6 (( 1 ( 2,2,2 TRIFLUOROETHYL)PIPERIDIN 4 YL)METHYL)THIENO[ 2,3 D]PYRIMIDIN 2 YL)PYRIMIDIN 2 AMINE; 5 ( 4 MORPHOLINOTHIENO[ 2,3 D]PYRIMIDIN 2 YL)PYRIMIDIN 2 AMINE; 5 ( 6 ( 3 (METHYLSULFONYL)PHENYL) 4 MORPHOLINOTHIENO[ 2,3 D]PYRIMIDIN 2 YL)PYRIMIDIN 2 AMINE; 5 ( 6 (( 1 (METHYLSULFONYL)PIPERIDIN 4 YL)METHYL) 4 MORPHOLINOTHIENO[ 2,3 D]PYRIMIDIN 2 YL)PYRIMIDIN 2 AMINE; 5 ( 6 (( 4 (METHYLSULFONYL)PIPERAZIN 1 YL)METHYL) 4 MORPHOLINOTHIENO[ 2,3 D]PYRIMIDIN 2 YL)PYRIMIDIN 2 AMINE; 5 ( 6 (( 4 (METHYLSULFONYL)PIPERIDIN 1 YL)METHYL) 4 MORPHOLINOTHIENO[ 2,3 D]PYRIMIDIN 2 YL)PYRIMIDIN 2 AMINE; 5 ( 6 (( 4 METHYLPIPERAZIN 1 YL)METHYL) 4 MORPHOLINOTHIENO[ 2,3 D]PYRIMIDIN 2 YL)PYRIMIDIN 2 AMINE; 8 BROMO 3,4 DIHYDROBENZO[B]OXEPIN 5 (2H) ONE; ARGININE; BENZOXEPIN DERIVATIVE; HYDROGEN; LIGAND; LYSINE; MORPHOLINE DERIVATIVE; N ( 2 CHLOROPHENYL) N METHYL 4,5 DIHYDROBENZO[B]THIENO[ 2,3 D]OXEPINE 2 CARBOXAMIDE; N ( 2 CHLOROPHENYL) N METHYL 8 (1H PYRAZOL 5 YL) 4,5 DIHYDROBENZO[B]THIENO[ 2,3 D]OXEPINE 2 CARBOXAMIDE; N (( 2 ( 2 AMINOPYRIMIDIN 5 YL) 4 MORPHOLINOTHIENO[ 2,3 D]PYRIMIDIN 6 YL)METHYL) N METHYLMETHANESULFONAMIDE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PHOSPHOINOSITIDE 3 KINASE ALPHA; PHOSPHOINOSITIDE 3 KINASE ALPHA INHIBITOR; PHOSPHOINOSITIDE 3 KINASE BETA; PHOSPHOTRANSFERASE; PIPERAZINE DERIVATIVE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AMINO ACID SUBSTITUTION; ANIMAL EXPERIMENT; ARTICLE; CELL PROLIFERATION; CHEMICAL ANALYSIS; CHEMICAL MODIFICATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG CLEARANCE; DRUG POTENCY; DRUG SELECTIVITY; DRUG TARGETING; HUMAN; HUMAN CELL; HYDROGEN BOND; IC 50; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PROTEIN PROTEIN INTERACTION; RAT; STATIC ELECTRICITY; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTINEOPLASTIC AGENTS; BENZOXEPINS; CELL LINE, TUMOR; CLASS I PHOSPHATIDYLINOSITOL 3-KINASES; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; HUMANS; HYDROGEN BONDING; ISOENZYMES; MICE; MODELS, MOLECULAR; PIPERAZINES; PROTEIN CONFORMATION; PYRIMIDINES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 81555223852     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2007084     Document Type: Article

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