Discovery and SAR of novel pyrazolo[1,5-a]pyrimidines as inhibitors of CDK9

Bioorganic and Medicinal Chemistry

Volumn 23, Issue 19, 2015, Pages 6280-6296

  Phillipson, Louisa J ^a,b   Segal, David H ^a,b   Nero, Tracy L ^c   Parker, Michael W ^c,d   Wan, Soo San ^a,b   De Silva, Melanie ^a,b   Guthridge, Mark A ^e   Wei, Andrew H ^e,f   Burns, Christopher J ^a,b,d  

^a WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c ST VINCENT'S INSTITUTE OF MEDICAL RESEARCH   (Australia)

^d UNIVERSITY OF MELBOURNE   (Australia)

^e MONASH UNIVERSITY   (Australia)

^f ALFRED HOSPITAL   (Australia)

Author keywords

CDK7; CDK9 selectivity; FLT3; Molecular modelling; PI3K ; Pyrazolo 1,5 a pyrimidine

Indexed keywords

2 CHLORO N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] N METHYL 5 NITROBENZENESULFONOHYDRAZIDE; 3 [[2 [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] 1 METHYLHYDRAZINYL]SULFONYL] 4 METHYLBENZAMIDE; 3 [[2 [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] 1 METHYLHYDRAZINYL]SULFONYL] 4 METHYLBENZOIC ACID; 3 [[2 [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] 1 METHYLHYDRAZINYL]SULFONYL] PYRIDINE 1 OXIDE; 5 BROMO N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] N,2 DIMETHYLBENZENESULFONOHYDRAZIDE; CYCLIN DEPENDENT KINASE 9; CYCLIN DEPENDENT KINASE INHIBITOR; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] 2 METHOXY N METHYL 5 NITROBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] 3 CYANO N METHYLBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] 3 FLUORO N METHYLBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] 3 METHOXY N METHYLBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] 3,4 DIFLUORO N METHYLBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] 4 FLUORO N METHYLBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] 5 CYANO N,2 DIMETHYLBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] 5 FLUORO N,2 DIMETHYLBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] N METHYL 3 (TRIFLUOROMETHOXY)BENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] N METHYL 3 NITROBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] N METHYL 4 NITROBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] N METHYLBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] N METHYLPYRIDINE 3 SULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] N,2 DIMETHYL 5 (METHYLSULFONYL)BENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] N,2 DIMETHYL 5 NITROBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] N,2 DIMETHYLBENZENESULFONOHYDRAZIDE; N' [(5 CHLOROPYRAZOLO[1,5 A]PYRIMIDIN 3 YL)METHYLENE] N,3 DIMETHYLBENZENESULFONOHYDRAZIDE; PIK 75; PROTEIN SERINE THREONINE KINASE INHIBITOR; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; ENZYME INHIBITOR; HYDRAZONE DERIVATIVE; PROTEIN BINDING; PYRAZOLE DERIVATIVE; PYRAZOLO(1,5-A)PYRIMIDINE; PYRIMIDINE DERIVATIVE; RECOMBINANT PROTEIN; SULFONAMIDE;

ARTICLE; CELL VIABILITY; CONTROLLED STUDY; DRUG BINDING; DRUG EFFECT; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME INHIBITION; HYDROPHOBICITY; IC50; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; ANTAGONISTS AND INHIBITORS; BINDING SITE; BIOSYNTHESIS; CELL LINE; CELL SURVIVAL; CHEMISTRY; DRUG EFFECTS; GENETICS; HUMAN; METABOLISM; MOLECULAR DOCKING; PRECLINICAL STUDY; PROTEIN TERTIARY STRUCTURE;

ANTINEOPLASTIC AGENTS; BINDING SITES; CELL LINE; CELL SURVIVAL; CYCLIN-DEPENDENT KINASE 9; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HUMANS; HYDRAZONES; MOLECULAR DOCKING SIMULATION; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; PYRAZOLES; PYRIMIDINES; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 84941944212     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2015.08.035     Document Type: Article

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