Substituted 4-(thiazol-5-yl)-2-(phenylamino)pyrimidines are highly active CDK9 inhibitors: Synthesis, X-ray crystal structures, structure-activity relationship, and anticancer activities

Journal of Medicinal Chemistry

Volumn 56, Issue 3, 2013, Pages 640-659

  Shao, Hao ^a   Shi, Shenhua ^a   Huang, Shiliang ^a   Hole, Alison J ^c   Abbas, Abdullahi Y ^a   Baumli, Sonja ^c   Liu, Xiangrui ^a   Lam, Frankie ^a,b   Foley, David W ^a   Fischer, Peter M ^a   Noble, Martin ^c,d   Endicott, Jane A ^c,d   Pepper, Chris ^e   Wang, Shudong ^a,b  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b UNIVERSITY OF SOUTH AUSTRALIA   (Australia)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d NEWCASTLE UNIVERSITY   (United Kingdom)

^e CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 [4 [3 [5 FLUORO 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL]PYRIMIDIN 2 YLAMINO]PHENYL]PIPERAZIN 1 YL]ETHANONE; 1 [4 [3 [[5 CHLORO 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL]PYRIMIDIN 2 YL]AMINO]PHENYL]PIPERAZIN 1 YL]ETHANONE; 2 [3 (1,4 DIAZEPAN 1 YL)PHENYLAMINO] 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL]PYRIMIDINE 5 CARBONITRILE; 2 [3 (4 ACETYL 1,4 DIAZEPAN 1 YL)PHENYLAMINO] 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL]PYRIMIDINE 5 CARBONITRILE; 2 [3 (4 ACETYLPIPERAZIN 1 YL)PHENYLAMINO] 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL]PYRIMIDINE 5 CARBONITRILE; 2 [4 (4 ACETYLPIPERAZIN 1 YL)PHENYLAMINO] 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL]PYRIMIDINE 5 CARBONITRILE; 3 [5 CYANO 4 (4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL]PYRIMIDIN 2 YLAMINO)BENZENESULFONAMIDE; 3 [[4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL] 5 PROPYLPYRIMIDIN 2 YL]AMINO]BENZENESULFONAMIDE; 3 [[5 CHLORO 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL]PYRIMIDIN 2 YL]AMINO]BENZENESULFONAMIDE; 3 [[5 ETHYL 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL]PYRIMIDIN 2 YL]AMINO]BENZENESULFONAMIDE; 3 [[5 HYDROXY 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL]PYRIMIDIN 2 YL]AMINO]BENZENESULFONAMIDE; 3 [[5 METHYL 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL]PYRIMIDIN 2 YL]AMINO]BENZENESULFONAMIDE; 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL] 2 (3 NITROPHENYLAMINO)PYRIMIDINE 5 CARBONITRILE; 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL] 2 [(3NITROPHENYL)AMINO]PYRIMIDIN 5 OL; 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL] 2 [3 (PIPERAZIN 1 YL]PHENYLAMINO]PYRIMIDINE 5 CARBONITRILE; 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL] 2 [4 (PIPERAZIN 1YL)PHENYLAMINO]PYRIMIDINE 5 CARBONITRILE; 4 [4 METHYL 2 (METHYLAMINO)THIAZOL 5 YL] 2 [[3 (PIPERIDIN 1 YL)PHENYL]AMINO]PYRIMIDINE 5 CARBONITRILE; 5 [2 [[5 (1,4 DIAZEPAN 1 YL) 2 FLUOROPHENYL]AMINO]PYRIMIDIN 4 YL] N,4 DIMETHYLTHIAZOL 2 AMINE; 5 [5 CHLORO 2 [[3 (PIPERAZIN 1 YL)PHENYL]AMINO]PYRIMIDIN 4 YL] N,4 DIMETHYLTHIAZOL 2 AMINE; 5 [5 FLUORO 2 [(3 MORPHOLINOPHENYL)AMINO]PYRIMIDIN 4 YL] N,4 DIMETHYLTHIAZOL 2 AMINE; 5 [5 FLUORO 2 [3 (PIPERAZIN 1 YL)PHENYLAMINO]PYRIMIDIN 4 YL] N,4 DIMETHYLTHIAZOL 2 AMINE; ANTINEOPLASTIC AGENT; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE 2 INHIBITOR; CYCLIN DEPENDENT KINASE 9; CYCLIN DEPENDENT KINASE INHIBITOR; PROTEIN MCL 1; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CELL MEDIATED CYTOTOXICITY; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG SYNTHESIS; EX VIVO STUDY; GENE MUTATION; HINGE REGION; HUMAN; HUMAN CELL; HYDROGEN BOND; IC 50; LEUKEMIA CELL; POLYMERIZATION; PROTEIN EXPRESSION; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; CYCLIN-DEPENDENT KINASE 9; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN KINASE INHIBITORS; PYRIMIDINES; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84873935155     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm301475f     Document Type: Article

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