Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro- N 2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)- N 4-(2-(isopropylsulfonyl) phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials

Journal of Medicinal Chemistry

Volumn 56, Issue 14, 2013, Pages 5675-5690

  Marsilje, Thomas H ^a   Pei, Wei ^a   Chen, Bei ^a   Lu, Wenshuo ^a   Uno, Tetsuo ^a   Jin, Yunho ^a   Jiang, Tao ^a   Kim, Sungjoon ^a   Li, Nanxin ^a   Warmuth, Markus ^a   Sarkisova, Yelena ^a   Sun, Frank ^a   Steffy, Auzon ^a   Pferdekamper, Annemarie C ^a   Li, Allen G ^a   Joseph, Sean B ^a   Kim, Young ^a   Liu, Bo ^a   Tuntland, Tove ^a   Cui, Xiaoming ^a   Gray, Nathanael S ^a   Steensma, Ruo ^a   Wan, Yongqin ^a   Jiang, Jiqing ^a   Chopiuk, Greg ^a   Li, Jie ^a   Gordon, W Perry ^a   Richmond, Wendy ^a   Johnson, Kevin ^a   Chang, Jonathan ^a   Groessl, Todd ^a   He, You Qun ^a   Phimister, Andrew ^a   Aycinena, Alex ^a   Lee, Christian C ^a   Bursulaya, Badry ^a   Karanewsky, Donald S ^a   Seidel, H Martin ^a   Harris, Jennifer L ^a   Michellys, Pierre Yves ^a   more..

^a GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [4 [4 [[5 CHLORO 4 [[2 (ISOPROPYLSULFONYL)PHENYL]AMINO]PYRIMIDIN 2 YL]AMINO] 5 ISOPROPOXY 2 METHYLPHENYL]PIPERIDIN 1 YL] 2 (DIMETHYLAMINO)ETHANONE; 2 [4 [4 [5 CHLORO 4 [2 (PROPANE 2 SULFONYL)PHENYLAMINO]PYRIMIDIN 2 YLAMINO] 5 ISOPROPOXY 2 METHYLPHENYL]PIPERIDIN 1 YL]ETHANOL; 2 [4 [4 [[5 CHLORO 4 [[2 (ISOPROPYLSULFONYL)PHENYL]AMINO]PYRIMIDIN 2 YL]AMINO] 5 ISOPROPOXY 2 METHYLPHENYL]PIPERIDIN 1 YL]ACETIC ACID; 2 [4 [5 ISOPROPOXY 4 [[4 [[2 (ISOPROPYLSULFONYL)PHENYL]AMINO] 5 METHYLPYRIMIDIN 2 YL]AMINO] 2 METHYLPHENYL]PIPERIDIN 1 YL]ETHANOL; 2 [[5 CHLORO 2 [[2 ISOPROPOXY 5 METHYL 4 (1 METHYLPIPERIDIN 4 YL)PHENYL]AMINO]PYRIMIDIN 4 YL]AMINO] N,N DIMETHYLBENZENESULFONAMIDE; 4 [4 [[5 CHLORO 4 [[2 (ISOPROPYLSULFONYL)PHENYL]AMINO]PYRIMIDIN 2 YL]AMINO] 5 ISOPROPOXY 2 METHYLPHENYL]PIPERIDIN 2 ONE; 5 CHLORO N2 [2 ISOPROPOXY 4 [1 (2 METHOXYETHYL)PIPERIDIN 4 YL] 5 METHYLPHENYL] N4 [2 (ISOPROPYLSULFONYL)PHENYL]PYRIMIDINE 2,4 DIAMINE; 5 CHLORO N2 [2 ISOPROPOXY 5 METHYL 4 (1 ETHYLPIPERIDIN 4 YL)PHENYL] N4 [2 (ISOPROPYLSULFONYL)PHENYL]PYRIMIDINE 2,4 DIAMINE; 5 CHLORO N2 [2 ISOPROPOXY 5 METHYL 4 (1 ISOPROPYLPIPERIDIN 4 YL)PHENYL] N4 [2 (ISOPROPYLSULFONYL)PHENYL]PYRIMIDINE 2,4 DIAMINE; 5 CHLORO N2 [2 ISOPROPOXY 5 METHYL 4 (1 METHYLPIPERIDIN 4 YL)PHENYL] N4 [2 (ISOPROPYLSULFONYL)PHENYL]PYRIMIDINE 2,4 DIAMINE; 5 CHLORO N2 [2 ISOPROPOXY 5 METHYL 4 (PIPERIDIN 4 YL)PHENYL] N4 [2 (ISOPROPYLSULFONYL)PHENYL]PYRIMIDINE 2,4 DIAMINE; 5 CHLORO N2 [2 ISOPROPOXY 5 METHYL 4 [1 (1 METHYLPIPERIDIN 4 YL)PIPERIDIN 4 YL]PHENYL] N4 [2 (ISOPROPYLSULFONYL)PHENYL]PYRIMIDINE 2,4 DIAMINE; 5 CHLORO N2 [4 [1 (2,2 DIFLUOROETHYL)PIPERIDIN 4 YL] 2 ISOPROPOXY 5 METHYLPHENYL] N4 [2 (ISOPROPYLSULFONYL)PHENYL]PYRIMIDINE 2,4 DIAMINE; 5 CHLORO N2 [4 ISOPROPOXY 2 (PIPERIDIN 4 YL)PYRIMIDIN 5 YL] N4 [2 (ISOPROPYLSULFONYL)PHENYL]PYRIMIDINE 2,4 DIAMINE; ANAPLASTIC LYMPHOMA KINASE; LDK 378; N2 [2 ISOPROPOXY 5 METHYL 4 (1 ETHYLPIPERIDIN 4 YL)PHENYL] N4 [2 (ISOPROPYLSULFONYL)PHENYL] 5 METHYLPYRIMIDINE 2,4 DIAMINE; N2 [2 ISOPROPOXY 5 METHYL 4 (1 METHYLPIPERIDIN 4 YL)PHENYL] N4 [2 (ISOPROPYLSULFONYL)PHENYL] 5 METHYLPYRIMIDINE 2,4 DIAMINE; N2 [2 ISOPROPOXY [1 (2 METHOXYETHYL)PIPERIDIN 4 YL] 5 METHYLPHENYL] N4 [2 (ISOPROPYLSULFONYL)PHENYL] 5 METHYLPYRIMIDINE 2,4 DIAMINE; PROTEIN TYROSINE KINASE INHIBITOR; PYRIMIDINE DERIVATIVE; STAT3 PROTEIN; TAE 684; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DESIGN; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SYNTHESIS; EXPERIMENTAL DOG; EXPERIMENTAL MONKEY; HUMAN; HUMAN CELL; IN VIVO STUDY; LIVER MICROSOME METABOLISM; MALE; MAXIMUM PLASMA CONCENTRATION; MOLECULAR DOCKING; MOLECULAR MODEL; MOUSE; NONHUMAN; PLASMA CLEARANCE; PROTEIN DOMAIN; RAT; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION; TUMOR XENOGRAFT;

ANIMALS; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; DOGS; HUMANS; MACACA FASCICULARIS; MALE; NEOPLASMS; PROTEIN KINASE INHIBITORS; PYRIMIDINES; RATS; RECEPTOR PROTEIN-TYROSINE KINASES; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84880877176     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400402q     Document Type: Article

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