Thienopyrimidine inhibitors of atypical protein kinase C

1. A method of treating a cancer in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula I or a pharmaceutically acceptable salt form thereof, wherein Formula I is:

wherein,

R 1 , R 2 , and R 11 are independently chosen from H and C 1-6 alkyl optionally substituted by 1-13 R 19 ;

R 3 is chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 7-11 arylalkyl optionally substituted by 1-9 R 19 , C 6-7 cycloalkylalkyl optionally substituted by 1-6 R 19 , and 6-11 membered heteroarylalkyl optionally substituted by 1-7 R 19 ;

R 4 , R 5 , and R 6 are H;

R 7 is selected from H and C 1-6 alkyl optionally substituted by 1-3 R 19 ;

R 8 is selected from C 2-6 alkynyl optionally substituted by 1-3 R 19 ;

R 12 , R 13 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —NR 42 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —OR 20 , and —S(═O) 2 NR 22 R 23 .

R 19 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, halogen, —C(═O)OR 30 and —OR 30 ; and

R 20 , R 22 , R 23 R 24 and R 30 at each occurrence are independently chosen from H and C 1-6 alkyl; and

wherein the cancer is selected from squamous cell carcinoma, leukemia, prostate cancer, non-Hodgkin's lymphoma, endometrial cancer, lung cancer and breast cancer; and

wherein treating a cancer refers to acute diminishment or alleviation of at least one symptom or characteristic associated or caused by the cancer being treated.

2. The method according to claim 1 wherein the lung cancer is non-small cell lung cancer.

3. The method according to claim 1 wherein the squamous cell carcinoma is esophageal squamous cell carcinoma.

4. The method according to claim 1 wherein the non-Hodgkin's lymphoma is follicular lymphoma.

5. The method according to claim 1 wherein R 1 , R 2 and R 11 are H.

6. The method according to claim 1 wherein R 3 is selected from C 1-6 alkyl optionally substituted by 1-13 R 19 and C 7-11 arylalkyl optionally substituted by 1-9 R 19 .

7. The method according to claim 1 wherein R 7 is H.

8. The method according to claim 1 wherein R 19 is selected from C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, halogen and —OR 30 .

9. The method according to claim 1 wherein R 12 , R 13 , R 14 , and R 15 are independently chosen from H and halogen.

10. The method according to claim 1 wherein the compound of formula I is selected from the group consisting of:

Structure

Name

(S)-N*1*-[7-(3-Methoxy-prop-1- ynyl)-2-pyridin-4-yl-thieno[3,2- d]pyrimidin-4-yl]-3-phenyl-propane- 1,2-diamine

4-[4-((S)-2-Amino-3-phenyl- propylamino)-2-(3-fluoro-pyridin-4- yl)-thieno[3,2-d]pyrimidin-7-yl]- but-3-yn-1-ol

4-[4-((S)-2-Amino-3-phenyl- propylamino)-6-methyl-2-pyridin-4- yl-thieno[3,2-d]pyrimidin-7-yl]-2- methyl-but-3-yn-2-ol

4-[4-((S)-2-Amino-3-phenyl- propylamino)-6-tert-butyl-2-pyridin- 4-yl-thieno[3,2-d]pyrimidin-7-yl]-2- methyl-but-3-yn-2-ol

3-[4-((S)-2-Amino-3-phenyl- propylamino)-2-(3-fluoro-pyridin-4- yl)-thieno[3,2-d]pyrimidin-7-yl]- prop-2-yn-1-ol

1-[4-((S)-2-Amino-3-phenyl- propylamino)-2-(3-fluoro-pyridin-4- yl)-thieno[3,2-d]pyrimidin-7- ylethynyl]-cyclobutanol

(S)-4-[4-((S)-2-Amino-3-phenyl- propylamino)-2-(3-fluoro-pyridin-4- yl)-thieno[3,2-d]pyrimidin-7-yl]- but-3-yn-2-ol

4-[4-((S)-2-Amino-3-phenyl- propylamino)-2-(3-fluoro-pyridin-4- yl)-thieno[3,2-d]pyrimidin-7-yl]-2- methyl-but-3-yn-2-ol

4-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-2- methyl-but-3-yn-2-ol

4-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-but-3- yn-2-ol

3-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-prop-2- yn-1-ol

S)-1-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-pent-1- yn-3-ol

(S)-1-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-4- methyl-hept-1-yn-3-ol

(S)-1-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-3- methyl-pent-1-yn-3-ol

(S)-1-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-3,4- dimethyl-pent-1-yn-3-ol

1-[4-(2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-3- ethyl-pent-1-yn-3-ol

(S)-1-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-hex-1- yn-3-ol

1-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-ylethynyl]- cyclopentanol

4-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-but-3- yn-1-ol

1-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-ylethynyl]- cyclopropanol

(S)-4-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-but-3- yn-2-ol

(R)-4-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-but-3- yn-2-ol

5-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-pent-4- yn-1-ol

5-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-pent-4- yn-2-ol

5-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-2- methyl-pent-4-yn-2-ol

1-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-ylethynyl]- cyclobutanol

(S)-5-[4-((S)-2-Amino-3-phenyl- propylamino)-2-pyridin-4-yl- thieno[3,2-d]pyrimidin-7-yl]-pent-4- yn-2-ol

(S)-N*1*-[7-((R)-3-Fluoro-but-1- ynyl)-2-pyridin-4-yl-thieno[3,2- d]pyrimidin-4-yl]-3-phenyl-propane- 1,2-diamine

(S)-N*1*-[7-(3-Fluoro-prop-1- ynyl)-2-pyridin-4-yl-thieno[3,2- d]pyrimidin-4-yl]-3-phenyl-propane- 1,2-diamine

(S)-N*1*-[7-(4-Fluoro-but-1-ynyl)- 2-pyridin-4-yl-thieno[3,2- d]pyrimidine .

11. The method according to claim 1 , wherein the cancer is squamous cell carcinoma.

12. The method according to claim 1 , wherein the cancer is leukemia.

13. The method according to claim 1 , wherein the cancer is prostate cancer.

14. The method according to claim 1 , wherein the cancer is non-Hodgkin's lymphoma.

15. The method according to claim 1 , wherein the cancer is endometrial cancer.

16. The method according to claim 1 , wherein the cancer is lung cancer.

17. The method according to claim 1 , wherein the cancer is breast cancer.

18. The method according to claim 1 , wherein R 11 is H.

19. The method according to claim 1 , wherein R 1 and R 2 are H.