Aurora kinase inhibitors for inhibiting mitotic progression

#1. Field of the Invention

#This invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides a compound that inhibits Aurora kinase enzymes, pharmaceutical compositions comprising the compound, and methods of using the compound for the treatment of cancer.

#2. Background of the Invention

#Claiborne et al., International Patent Publication WO 05/111039, discloses pyrimidobenzazepine compounds with Aurora kinase inhibitory activity. The present inventors have now discovered pyrimidobenzazepine compounds with unexpectedly superior potency against Aurora A kinase. The claimed compounds are useful for inhibiting Aurora A kinase activity in vitro and in vivo, and are especially useful for the treatment of various cell proliferative diseases.

#In one aspect, therefore, the invention provides a compound represented by formula (I):

#or a pharmaceutically acceptable salt thereof, wherein: Ra is selected from the group consisting of C1-3 aliphatic, C1-3 fluoroaliphatic, —R1, -T-R1, —R2, and -T-R2; T is a C1-3 alkylene chain optionally substituted with fluoro; R1 is an optionally substituted aryl, heteroaryl, or heterocyclyl group; R2 is selected from the group consisting of halo, —C≡C—R3, —CH═CH—R3, —N(R4)2, and —OR5; R3 is hydrogen or an optionally substituted aliphatic, aryl, heteroaryl, or heterocyclyl group; each R4 independently is hydrogen or an optionally substituted aliphatic, aryl, heteroaryl, or heterocyclyl group; or two R4 on the same nitrogen atom, taken together with the nitrogen atom form an optionally substituted 5- to 6-membered heteroaryl or 4- to 8-membered heterocyclyl ring having, in addition to the nitrogen atom, 0-2 ring heteroatoms selected from N, O, and S; R5 is hydrogen or an optionally substituted aliphatic, aryl, heteroaryl, or heterocyclyl group; and Rb is selected from the group consisting of fluoro, chloro, —CH3, —CF3, —OH, —OCH3, —OCF3, —OCH2CH3, and —OCH2CF3.