4,5-Dihydro-1H-pyrazolo[4,3-h]quinazolines as potent and selective Polo-like kinase 1 (PLK1) inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 22, 2010, Pages 6489-6494

  Beria, Italo ^a   Valsasina, Barbara ^a   Brasca, Maria Gabriella ^a   Ceccarelli, Walter ^a   Colombo, Maristella ^a   Cribioli, Sabrina ^a   Fachin, Gabriele ^a   Ferguson, Ronald D ^a,b   Fiorentini, Francesco ^b   Gianellini, Laura M ^a   Giorgini, Maria L ^a   Moll, Jurgen K ^a   Posteri, Helena ^a   Pezzetta, Daniele ^b   Roletto, Fulvia ^a   Sola, Francesco ^a   Tesei, Dania ^a   Caruso, Michele ^a  

^a NERVIANO MEDICAL SCIENCES   (Italy)

^b Accelera   (Italy)

Author keywords

In vivo activity; Kinase inhibitor; PLK1; Polo like kinase

Indexed keywords

ANTINEOPLASTIC AGENT; CISPLATIN; CYCLIN DEPENDENT KINASE 2; DOXORUBICIN; PACLITAXEL; POLO LIKE KINASE 1; POLO LIKE KINASE 2; POLO LIKE KINASE 3; PROTEIN SERINE THREONINE KINASE INHIBITOR; PYRAZOLE DERIVATIVE; QUINAZOLINE DERIVATIVE;

ANIMAL EXPERIMENT; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CHRONIC MYELOID LEUKEMIA; COLON ADENOCARCINOMA; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN CELL; IC 50; IN VIVO STUDY; LUNG NON SMALL CELL CANCER; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; OVARY CANCER; OVARY CARCINOMA; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELL CYCLE PROTEINS; CELL LINE, TUMOR; HUMANS; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; QUINAZOLINES; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSPLANTATION, HETEROLOGOUS;

EID: 77958028231     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.09.060     Document Type: Article

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17. The panel includes c-ABL, AKT1, Aur-A, Aur-B, CDC7, CDK1/B, CDK2/E, CDK4/D1, CDK5/P25, CHK1, EGFR1, ERK2, FGFR1, GSK3β IGF1R, IKK2, IR, JAK2, KIT, LCK, MAP-KAPK2, MET, MPS1, STK2, NIM, P38α, P38β, PAK4, PDK1, PKAα, PKCβ, RET, TAO3, TRKA, VEGFR2, VEGFR3 and, ZAP70.
18. Human liver microsomes was carried out as previously reported Ref. 12.
19. High-throughput solubility was carried out as previously reported Ref. 12.
20. The pharmacokinetic profiles of the compounds were investigated in overnight fasted male CD1 nu/nu mice following a single dose given intravenously (iv) or orally (po). Blood samples of each mouse were taken from saphenous vein at different time and after centrifugation plasma samples were analyzed by LC/MS/MS technique. For a more complete description see Ref. 12.