Methods of using ALK inhibitors
View Patent ↗The invention provides methods for using compounds of Formula (I) for treating an EML4-ALK + mediated condition such as EML4-ALK + non-small cell lung cancer, and optionally resistant to crizotinib; wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined above.
1. A method for treating EML4-ALK + mediated non-small cell lung cancer that is optionally resistant to crizotinib, comprising administering to a cell or subject a compound of Formula (I)
or a pharmaceutically acceptable salt thereof;
wherein R 1 is halo;
R 2 is H; or
wherein R 1 and R 2 together with the carbon atoms to which they are attached form a 5-6 membered heteroaryl comprising 1-2 heteroatoms selected from N, O and S;
R 3 is SO 2 R 7 wherein R 7 is C 1-6 alkyl;
R 4 is C 1-6 alkoxy;
R 5 is piperidinyl optionally substituted with C 1-6 alkyl;
R 6 is C 1-6 alkyl; or
R 5 and R 6 together with the carbon atoms to which they are attached form a 5-6 membered heterocyclic ring comprising having 1-2 heteroatoms selected from N, O and S.
2. The method according to claim 1 , wherein the EML4-ALK + mediated non-small cell lung cancer is resistant to crizotinib.
3. The method of claim 1 , wherein R 1 in Formula (I) is chloro.
4. The method of claim 1 , wherein R 4 in Formula (I) is isopropoxy.
5. The method of claim 1 , wherein R 5 and R 6 together with the carbon atoms to which they are attached form —CH 2 —NR 8 —C(O)—, wherein R 8 is hydrogen or piperidinyl, optionally substituted with C 1-6 alkyl.
6. The method of claim 1 , wherein said compound of Formula (I) is selected from the group:
5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-2-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
(S)-5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-2-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
(R)-5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-2-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine;
5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-3-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine; and
6-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-5-isopropoxy-2-(1-methyl-piperidin-4-yl)-2,3-dihydro-isoindol-1-one;
or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein said compound is 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine.
8. The method of claim 6 , wherein said compound is 6-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-5-isopropoxy-2-(1-methyl-piperidin-4-yl)-2,3-dihydro-isoindol-1-one.
9. The method of claim 1 , wherein said subject is a human or animal subject.