3-Cyano-6-(5-methyl-3-pyrazoloamino)pyridines: selective Aurora A kinase inhibitors.
A new class of Aurora A kinase inhibitor was created by transforming 4-(5-methyl-3-pyrazoloamino)pyrimidine moiety of VX-680 to 3-cyano-6-(5-methyl-3pyrazoloamino)pyridine. Compound 6 exhibited a potent Aurora A kinase inhibitory activity, excellent selectivity to Aurora B kinase and other 60 kinases, good cell permeability and good PK profile. Therefore compound 6 was effective in antitumor mice model at a dose of 30 mg/kg po qd without decrease of body weight.
Ando
Ryoichi
R
Medicinal Chemistry Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Aoba-ku, Yokohama 227-0033, Japan.
Ikegami
Hiroshi
H
Sakiyama
Makoto
M
Ooike
Shinsuke
S
Hayashi
Masayuki
M
Fujino
Yasuhiro
Y
Abe
Daisuke
D
Nakamura
Hideo
H
Mishina
Tadashi
T
Kato
Harutoshi
H
Iwase
Yumiko
Y
Tomozane
Hideo
H
Morioka
Masahiko
M
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010879:Piperazines / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D023041:Xenograft Model Antitumor Assays; D003521:Cyclopropanes
D000970:Antineoplastic Agents; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; C553562:4-(5-methyl-3-pyrazoloamino)pyrimidine; C484810:tozasertib; D003521:Cyclopropanes; C576921:AURKB protein, human; C576918:Aurka protein, mouse; C576920:Aurka protein, rat; C576924:Aurkb protein, mouse; C576925:Aurkb protein, rat