Benzazole derivatives, compositions, and methods of use as aurora kinase inhibitors

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein G2 is substituted with at least one substituent selected from the group consisting of: halo, phenyl, C1-10 alkyl, piperazine-1-yl, 4-(C1-10 alkyl)-piperazine-1-yl, C1-10 alkoxy, haloalkyl, cycloalkyl, and C1-10 alkylene-cycloalkyl.

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein G2 is phenyl, naphthyl, isoquinolin-3-yl, pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiazole-2-yl, imidazole-2-yl or benzothiazole-2-yl,nwherein G2 is unsubstituted or substituted with at least one substituent selected from the group consisting of: chloro, fluoro, methyl, ethyl, propyl, isopropyl, tert-butyl, butyl, phenyl, methoxy, trifluoromethyl, trifluoromethoxy, and cyclopentyl.

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein G1 is unsubstituted or substituted with at least one group selected from the group consisting of: halo, phenyl, C1-10 alkyl, piperazine-1-yl, 4-(C1-10 alkyl)-piperazine-1-yl, —C1-10 alkoxy, —C1-10 alkylene-OH, -haloalkyl, -cycloalkyl, —C1-10 alkylene-cycloalkyl, morpholine-4-yl, —C1-10-alkylene-morpholine-4-yl, pyrrole-1-yl, -amino, —NH—(C1-10 alkyl), —N(C1-10 alkyl)2, —NHC(O)—C1-10 alkyl, —NHC(O)-(1-(C1-10 alkyl)-piperidine-4-yl), —NHC(O)-phenyl, —NH—C1-10 alkylene-morpholine-4-yl, —O—C1-10 alkylene-morpholine-4-yl, and —NH—C1-10 alkylene-OH.

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein G1 is 1H-indazole-5-yl or 1H-indazole-6-yl,nwherein G1 is unsubstituted or substituted at the 3-position with a substituent selected from the group consisting of: halo, phenyl, C1-10 alkyl, piperazine-1-yl, 4-(C1-10 alkyl)-piperazine-1-yl, —C1-10 alkoxy, —C1-10 alkylene-OH, -haloalkyl, -cycloalkyl, —C1-10 alkylene-cycloalkyl, morpholine-4-yl, —C1-10-alkylene-morpholine-4-yl, pyrrole-1-yl, -amino, —NH—(C1-10 alkyl), —N(C1-10 alkyl)2, —NHC(O)—C1-10 alkyl, —NHC(O)-(1-(C1-10 alkyl)-piperidine-4-yl), —NHC(O)-phenyl, —NH—C1-10 alkylene-morpholine-4-yl, —O—C1-10 alkylene-morpholine-4-yl, and —NH—C1-10 alkylene-OH.

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, whereinnu is 1,A is a direct bond, andQ is selected from the group consisting of: 4-(C1-10 alkyl)-piperazine-1-yl, piperadine-1-yl, morpholine-4-yl, —NH—C1-10 alkyl, —N—(C1-10 alkyl)2, —N—(C1-10 alkyl)(cycloalkyl), and —NH-cycloalkyl.

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein u is zero and v is zero.

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein u is 1 and v is zero.

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein u is zero and v is one.

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, whereinnu is zero,v is one, andR1 is selected from the group consisting of: —C1-10 alkyl, -cycloalkyl, —C1-10 alkylene-cycloalkyl, —C1-10 haloalkyl, -phenyl, —O—C1-10 alkyl, —O-cycloalkyl, and —O—C1-10 haloalkyl.

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, whereinnX is —NH—,E is —NH—,v is zero,L1 is —NHC(O)— or —C(O)NH—,G1 is 1H-indazol-6-yl or 1H-indazol-5-yl,nwherein G1 is optionally substituted 1-4 times with a substituent selected from the group consisting of Rb.

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof having the formula:

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof having the formula:

The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof having the formula:

The compound of Formula (I) in claim 1 selected from the group consisting of: 4-[6-(1H-Indazol-6-ylcarbamoyl)-2-(2-trifluoromethylphenylamino)-3H-benzimidazol-5-yl]-piperazine-1-carboxylic acid tert-butyl ester,n6-piperazin-1-yl-2-(2-trifluoromethylphenylamino)-1H-benzimidazole-5-carboxylic acid (1H-indazol-6-yl)-amide,4-[6-(1H-Indazol-6-ylcarbamoyl)-2-(3-methylpyridin-2-ylamino)-3H-benzimidazol-5-yl]-piperazine-1-carboxylic acid tert-butyl ester, and2-(3-Methylpyridin-2-ylamino)-6-piperazin-1-yl-1H-benzimidazole-5-carboxylic acid (1H-indazol-6-yl)-amide,or a pharmaceutically acceptable salt thereof.

A pharmaceutical composition comprising a compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

The pharmaceutical composition of claim 27, wherein the pharmaceutical composition is in the form of a liposome.