P
USRE48635EActiveUtilityPatentIndex 59

ERK inhibitors

Assignee: LILLY CO ELIPriority: Dec 22, 2014Filed: May 22, 2019Granted: Jul 13, 2021
Est. expiryDec 22, 2034(~8.5 yrs left)· nominal 20-yr term from priority
Inventors:CORTEZ GUILLERMO SJOSEPH SAJANMCLEAN JOHNATHAN ALEXANDERMCMILLEN WILLIAM TRODRIGUEZ MICHAEL JOHNZHAO GAIYING
C07D 498/08A61P 35/00C07D 513/04C07D 495/04A61K 39/3955A61K 31/5377A61K 31/506C07K 16/2863A61K 31/519
59
PatentIndex Score
0
Cited by
7
References
42
Claims

Abstract

The present invention provides thieno[2,3-c]pyrrol-4-one compounds that inhibit activity of extracellular-signal-regulated kinase (ERK) and may be useful in the treatment of cancer.

Claims

exact text as granted — not AI-modified
We claim: 
     
       1. A compound of the formula: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  is 
 
       
       
         
           
           
               
               
           
         
         
           R 2  and R 3  are methyl or R 2  and R 3  can be taken together to form cyclopropyl; 
           R 4  is hydrogen, methyl, chloro, fluoro, or trifluoromethyl; and 
           R 5  is 
         
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       2. The compound or salt according to  claim 1  wherein R 2  and R 3  are independently methyl. 
     
     
       3. The compound or salt according to  claim 2  wherein R 4  is hydrogen. 
     
     
       4. The compound or salt according to  claim 3  wherein R 1  is 
       
         
           
           
               
               
           
         
       
     
     
       5. The compound or salt according to  claim 3  wherein R 5  is 
       
         
           
           
               
               
           
         
       
     
     
       6. The compound or salt according to  claim 4  which is 6,6-dimethyl-2-{2-[(1-methyl-1H-pyrazol-5-yl)amino]pyrimidin-4-yl}-5-[2-(morpholin-4-yl)ethyl]-5,6-dihydro-4H-thieno[2,3-c]pyrrol-4-one or a pharmaceutically acceptable salt thereof. 
     
     
       7. The compound according to  claim 6  which is 6,6-dimethyl-2-{2-[(1-methyl-1H-pyrazol-5-yl)amino]pyrimidin-4-yl}-5-[2-(morpholin-4-yl)ethyl]-5,6-dihydro-4H-thieno[2,3-c]pyrrol-4-one. 
     
     
       8. A pharmaceutical composition comprising a compound of the formula: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  is 
 
       
       
         
           
           
               
               
           
         
         
           R 2  and R 3  are methyl or R 2  and R 3  can be taken together to form cyclopropyl; 
           R 4  is hydrogen, methyl, chloro, fluoro, or trifluoromethyl; and 
           R 5  is 
         
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. 
       
     
     
       9. The pharmaceutical composition according to  claim 8  wherein R 2  and R 3  are independently methyl. 
     
     
       10. The pharmaceutical composition according to  claim 9  wherein R 4  is hydrogen. 
     
     
       11. The pharmaceutical composition according to  claim 10  wherein R 1  is 
       
         
           
           
               
               
           
         
       
     
     
       12. The pharmaceutical composition according to  claim 10  wherein R 5  is 
       
         
           
           
               
               
           
         
       
     
     
       13. The A pharmaceutical composition according to  claim 11  which is comprising 6,6-dimethyl-2-{2-[(1-methyl-1H-pyrazol-5-yl)amino]pyrimidin-4-yl}-5-[2-(morpholin-4-yl)ethyl]-5,6-dihydro-4H-thieno[2,3-c]pyrrol-4-one, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. 
     
     
       14. The pharmaceutical composition according to  claim 13  which is comprising 6,6-dimethyl-2-{2-[(1-methyl-1H-pyrazol-5-yl)amino]pyrimidin-4-yl}-5-[2-(morpholin-4-yl)ethyl]-5,6-dihydro-4H-thieno[2,3-c]pyrrol-4-one, and a pharmaceutically acceptable carrier, diluent, or excipient. 
     
     
       15. A method of treating cancer, comprising administering to a patient in need thereof, an effective amount of a compound of the formula: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  is 
 
       
       
         
           
           
               
               
           
         
         
           R 2  and R 3  are methyl or R 2  and R 3  can be taken together to form cyclopropyl; 
           R 4  is hydrogen, methyl, chloro, fluoro, or trifluoromethyl; and 
           R 5  is 
         
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein the cancer is selected from the group consisting of melanoma, colorectal cancer, pancreatic cancer, and non-small cell lung cancer. 
       
     
     
       16. The method according to  claim 15  wherein R 2  and R 3  are independently methyl. 
     
     
       17. The method according to  claim 16  wherein R 4  is hydrogen. 
     
     
       18. The method according to  claim 17  wherein R 1  is 
       
         
           
           
               
               
           
         
       
     
     
       19. The compound or salt method according to  claim 17  wherein R 5  is 
       
         
           
           
               
               
           
         
       
     
     
       20. The compound or salt method according to  claim 18  which wherein the compound is 6,6-dimethyl-2-{2-[(1-methyl-1H-pyrazol-5-yl)amino]pyrimidin-4-yl}-5-[2-(morpholin-4-yl)ethyl]-5,6-dihydro-4H-thieno[2,3-c]pyrrol-4-one or a pharmaceutically acceptable salt thereof. 
     
     
       21. The compound method according to  claim 20  which wherein the compound is 6,6-dimethyl-2-{2-[(1-methyl-1H-pyrazol-5-yl)amino]pyrimidin-4-yl}-5-[2-(morpholin-4-yl)ethyl]-5,6-dihydro-4H-thieno[2,3-c]pyrrol-4-one. 
     
     
       22. The method according to  claim 15 , wherein the cancer is colorectal cancer. 
     
     
       23. The method according to  claim 16 , wherein the cancer is colorectal cancer. 
     
     
       24. The method according to  claim 17 , wherein the cancer is colorectal cancer. 
     
     
       25. The method according to  claim 18 , wherein the cancer is colorectal cancer. 
     
     
       26. The method according to  claim 19 , wherein the cancer is colorectal cancer. 
     
     
       27. The method according to  claim 20 , wherein the cancer is colorectal cancer. 
     
     
       28. The method according to  claim 21 , wherein the cancer is colorectal cancer. 
     
     
       29. The method according to  claim 15 , wherein the cancer is pancreatic cancer. 
     
     
       30. The method according to  claim 16 , wherein the cancer is pancreatic cancer. 
     
     
       31. The method according to  claim 17 , wherein the cancer is pancreatic cancer. 
     
     
       32. The method according to  claim 18 , wherein the cancer is pancreatic cancer. 
     
     
       33. The method according to  claim 19 , wherein the cancer is pancreatic cancer. 
     
     
       34. The method according to  claim 20 , wherein the cancer is pancreatic cancer. 
     
     
       35. The method according to  claim 21 , wherein the cancer is pancreatic cancer. 
     
     
       36. The method according to  claim 15 , wherein the cancer is non-small cell lung cancer. 
     
     
       37. The method according to  claim 16 , wherein the cancer is non-small cell lung cancer. 
     
     
       38. The method according to  claim 17 , wherein the cancer is non-small cell lung cancer. 
     
     
       39. The method according to  claim 18 , wherein the cancer is non-small cell lung cancer. 
     
     
       40. The method according to  claim 19 , wherein the cancer is non-small cell lung cancer. 
     
     
       41. The method according to  claim 20 , wherein the cancer is non-small cell lung cancer. 
     
     
       42. The method according to  claim 21 , wherein the cancer is non-small cell lung cancer.

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