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Generated: September 23, 2017

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Title:Methods of using ALK inhibitors
Abstract: The invention provides methods for using compounds of Formula (I) for treating an EML4-ALK.sup.+ mediated condition such as EML4-ALK.sup.+ non-small cell lung cancer, and optionally resistant to crizotinib; wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are as defined above.
Inventor(s): Li; Nanxin (San Diego, CA), Harris; Jennifer Leslie (San Diego, CA), McNamara; Peter (San Diego, CA), Sun; Fangxian (Melrose, MA)
Assignee: IRM LLC (Hamilton, BM)
Application Number:13/981,046
Patent Claims: 1. A method for treating EML4-ALK.sup.+ mediated non-small cell lung cancer that is optionally resistant to crizotinib, comprising administering to a cell or subject a compound of Formula (I) ##STR00009## or a pharmaceutically acceptable salt thereof; wherein R.sup.1 is halo; R.sup.2 is H; or wherein R.sup.1 and R.sup.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.sup.3 is SO.sub.2R.sup.7 wherein R.sup.7 is C.sub.1-6 alkyl; R.sup.4 is C.sub.1-6 alkoxy; R.sup.5 is piperidinyl optionally substituted with C.sub.1-6 alkyl; R.sup.6 is C.sub.1-6 alkyl; or R.sup.5 and R.sup.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.sup.+ mediated non-small cell lung cancer is resistant to crizotinib.

3. The method of claim 1, wherein R.sup.1 in Formula (I) is chloro.

4. The method of claim 1, wherein R.sup.4 in Formula (I) is isopropoxy.

5. The method of claim 1, wherein R.sup.5 and R.sup.6 together with the carbon atoms to which they are attached form --CH.sub.2--NR.sup.8--C(O)--, wherein R.sup.8 is hydrogen or piperidinyl, optionally substituted with C.sub.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-(propa- ne-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine; 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-2-yl)phenyl)-N4-(2-(isopr- opylsulfonyl)phenyl)pyrimidine-2,4-diamine; (S)-5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-2-yl)phenyl)-N4-(2-(i- sopropylsulfonyl)phenyl)pyrimidine-2,4-diamine; (R)-5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-2-yl)phenyl)-N4-(2-(i- sopropylsulfonyl)phenyl)pyrimidine-2,4-diamine; 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-3-yl)phenyl)-N4-(2-(isopr- opylsulfonyl)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-(propa- ne-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.
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