Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA-793887, a potent CDK inhibitor suitable for intravenous dosing

Bioorganic and Medicinal Chemistry

Volumn 18, Issue 5, 2010, Pages 1844-1853

  Brasca, Maria Gabriella ^a   Albanese, Clara ^a   Alzani, Rachele ^a   Amici, Raffaella ^b   Avanzi, Nilla ^a   Ballinari, Dario ^a   Bischoff, James ^c   Borghi, Daniela ^a   Casale, Elena ^a   Croci, Valter ^a   Fiorentini, Francesco ^d   Isacchi, Antonella ^a   Mercurio, Ciro ^b   Nesi, Marcella ^a   Orsini, Paolo ^a   Pastori, Wilma ^a   Pesenti, Enrico ^a   Pevarello, Paolo ^e   Roussel, Patrick ^f   Varasi, Mario ^b   Volpi, Daniele ^a   Vulpetti, Anna ^g   Ciomei, Marina ^a   more..

^a NERVIANO MEDICAL SCIENCES   (Italy)

^b MIKAMAI Srl   (Italy)

^c Centro Nacional de Investigaciones Oncológicas   (Spain)

^d Accelera   (Italy)

^e Newron Pharmaceuticals   (Italy)

^f BASILEA PHARMACEUTICA INTERNATIONAL LTD   (Switzerland)

^g Novartis Pharma AG   (Switzerland)

Author keywords

Anti cancer; CDK; Cell cycle; Cyclin dependent kinases; Kinase; Kinase inhibitor; Tumor cell proliferation inhibition

Indexed keywords

4 CHLORO N [6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] BENZAMIDE; 6,6 DIMETHYLPYRROLO [3,4 C] PYRAZOLE DERIVATIVE; CYCLIN DEPENDENT KINASE INHIBITOR; N 6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YLNAPHTHALENE 1 CARBOXAMIDE; N 6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YLNAPHTHALENE 2 CARBOXAMIDE; N 6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YLPYRIDINE 4 CARBOXAMIDE; N 6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YLTHIOPHENE 2 CARBOXAMIDE; N [5 (1 ACETYLPIPERIDIN 4 YLCARBONYL) 6,6 DIMETHYL 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] 4 FLUOROBENZAMIDE; N [5 (1 CYCLOPROPYLPIPERIDIN 4 YLCARBONYL) 6,6 DIMETHYL 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] 4 FLUOROBENZAMIDE; N [5 (1 ETHYLPIPERIDIN 4 YLCARBONYL) 6,6 DIMETHYL 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] 4 FLUOROBENZAMIDE; N [5 (2,2 DIMETHYLPROPANOYL) 6,6 DIMETHYL 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] 1 METHYLPIPERIDINE 4 CARBOXAMIDE; N [5 (2,2 DIMETHYLPROPANOYL) 6,6 DIMETHYL 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] 3,5 DIFLUOROBENZAMIDE; N [5 (2,2 DIMETHYLPROPANOYL) 6,6 DIMETHYL 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] N2,N2 DIMETHYLGLYCINAMIDE; N [5 (2,2 DIMETHYLPROPANOYL) 6,6 DIMETHYL 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] PIPERIDINE 4 CARBOXAMIDE; N [5 (2,2 DIMETHYLPROPANOYL) 6,6 DIMETHYL 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] PYRIDINE 3 CARBOXAMIDE; N [5 (2,2 DIMETHYLPROPANOYL) 6,6 DIMETHYL 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] PYRIDINE 4 CARBOXAMIDE; N [5 (2,2 DIMETHYLPROPANOYL) 6,6 DIMETHYL-1,4,5,6-TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] 4 FLUOROBENZAMIDE; N [6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YL CARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] 3,5 DIFLUOROBENZAMIDE; N [6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] 3 FLUOROBENZAMIDE; N [6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] 3,4 DIFLUOROBENZAMIDE; N [6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] 4 FLUOROBENZAMIDE; N [6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] 4 TRIFLUOROMETHYLBENZAMIDE; N [6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] BENZAMIDE; N [6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] CYCLOBUTANCARBOXAMIDE; N [6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YLFURAN 2 CARBOXAMIDE; N [6,6 DIMETHYL 5 (1 METHYLPIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YLTHIOPHENE 3 CARBOXAMIDE; N [6,6 DIMETHYL 5 (PIPERIDIN 4 YLCARBONYL) 1,4,5,6 TETRAHYDROPYRROLO (3,4 C) PYRAZOL 3 YL] 4 FLUOROBENZAMIDE; PHA 793887; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER CELL; CANCER INHIBITION; COLON CARCINOMA; CONTROLLED STUDY; DOSE RESPONSE; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG PENETRATION; DRUG SCREENING; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERABILITY; FLOW CYTOMETRY; HUMAN; HUMAN CELL; HUMAN TISSUE; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; OVARY CARCINOMA; PANCREAS CARCINOMA; SOLID TUMOR; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS; BINDING SITES; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; CYCLIN-DEPENDENT KINASES; HCT116 CELLS; HUMANS; INJECTIONS, INTRAVENOUS; MICE; MICE, NUDE; PROTEIN KINASE INHIBITORS; PYRAZOLES; PYRROLES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 77249098663     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2010.01.042     Document Type: Article

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