3-Cyano-6-(5-methyl-3-pyrazoloamino)pyridines: Selective Aurora A kinase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 15, 2010, Pages 4709-4711

  Ando, Ryoichi ^a   Ikegami, Hiroshi ^a   Sakiyama, Makoto ^a   Ooike, Shinsuke ^a   Hayashi, Masayuki ^a   Fujino, Yasuhiro ^a   Abe, Daisuke ^a   Nakamura, Hideo ^a   Mishina, Tadashi ^a   Kato, Harutoshi ^a   Iwase, Yumiko ^a   Tomozane, Hideo ^a   Morioka, Masahiko ^a  

^a MITSUBISHI TANABE PHARMA CORPORATION   (Japan)

Author keywords

Aminopyrazole; Aurora kinase; Cyanopyridine

Indexed keywords

3 CYANO 6 (5 METHYL 3 PYRAZOLOAMINO)PYRIDINE; AURORA A KINASE; ENZYME INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BODY WEIGHT; CELL MEMBRANE PERMEABILITY; CONTROLLED STUDY; MOUSE; NONHUMAN;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; HUMANS; MICE; MICE, NUDE; PIPERAZINES; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; PYRAZOLES; PYRIDINES; PYRIMIDINES; RATS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

MUS;

EID: 77955418695     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.04.119     Document Type: Article

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11. All new compounds were fully characterized.
12. m value of kemptide was 28 μM.
13. 6O·HCl: C, 58.08; H, 7.44; N, 21.39. Found: C, 57.79; H, 7.47; N, 21.21.
14. int) in human hepatic microsomes of the racemate, the eutomer, and the distomer were 0.07, 0.05, and 0.11 mL/min/mg, respectively. Absolute configuration of the eutomer was (S)-form which was determined by chemical synthesis via an alternative route starting from (R)-6-methyl-5-hepten-2-ol.
15. i values against yes, cSRC, and Fyn inhibition were 24, 26, and 28 nM, respectively.
16. Growth inhibitions by VX-680 (30 and 100 mg/kg ip qd) after 14 days were 60% and 68%, respectively.