DGAT2 inhibitors

Patent metadata

Field	Value
Publication number	US-10053429-B2
Application number	US-201615571052-A
Country	US
Kind code	B2
Filing date	May 19, 2016
Priority date	May 20, 2015
Publication date	Aug 21, 2018
Grant date	Aug 21, 2018

Abstract

The present invention provides compounds of the Formula below: [Formula should be inserted here] Where A, X, R. and R2-R3 are as described herein; methods of treating patients for hypertriglyceridemia and cardiovascular disease including dyslipidemia and atherosclerosis, and processes for preparing the compounds.

First claim

What is claimed is:

1. A compound of Formula 1 below:

wherein:
X is CH or N;
A is CH or N, provided that at least one of X and A is N;
L is a —C 1-3 alkyl;
R is selected from: —S(O) 2 NHR4, —NHS(O) 2 R5, and —NHC(O)—R6;
R1 is H or halo;
R2 is selected from: H, —C 1-2 alkyl, —CN, —CF 3 , —NH 2 , —N(H)CH 3 , —N(CH 3 ) 2 , —OCH 3 , —CH 2 —O—CH 3 , —SCH 3 , -cyclopropyl, piperazinyl, 4-methyl piperazinyl, and morpholinyl;
R3 is selected from C 1-2 alkyl, halo, —CHF 2 , —CF 3 , and —OCH 3 ;
R4 is H or —CH 3 ;
R5 is selected from: —CH 3 , —NH 2 , and —NHCH 3 ;
R6 is selected from: —CH 3 , —CH 2 OH, —CH 2 OCH 3 , —CH(OH)CH 3 , —NH 2 , and —NHCH 3 ;
R7 is H or —CH 3 ;
provided that when R1 is H, R2 is Me, R3 is Cl, R7 is H, and X and A are both N, L-R is not —(CH 2 )S(O) 2 —NH 2 , or —(CH 2 )S(O) 2 —NHCH 3 , or

a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 wherein A is N, or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 1 wherein X is N or a pharmaceutically acceptable salt thereof.

4. A compound according to claim 1 wherein X is CH or a pharmaceutically acceptable salt thereof.

5. A compound according to claim 1 wherein L is —CH 2 — or —CH 2 CH 2 — or a pharmaceutically acceptable salt thereof.

6. A compound according to claim 1 wherein R is selected from —S(O) 2 NHR4 and —NH(SO) 2 R5 or a pharmaceutically acceptable salt thereof.

7. A compound according to claim 1 wherein R is —S(O) 2 NHR4 or a pharmaceutically acceptable salt thereof.

8. A compound according to claim 1 wherein R1 is H or a pharmaceutically acceptable salt thereof.

9. A compound according to claim 1 wherein R2 is selected from: H, —C 1-2 alkyl, —CN, —CF 3 , —NH 2 , —N(H)CH 3 , —N(CH 3 ) 2 , 4-methyl piperazinyl, and morpholinyl or a pharmaceutically acceptable salt thereof.

10. A compound according to claim 9 wherein R2 is selected from: H, —CH 3 , —NH 2 , —N(H)CH 3 , —N(CH 3 ) 2 , 4-methyl piperazinyl, and morpholinyl or a pharmaceutically acceptable salt thereof.

11. A compound according to claim 10 wherein R2 is selected from: H, —CH 3 , —NH 2 , and 4-methyl piperazinyl or a pharmaceutically acceptable salt thereof.

12. A compound according to claim 1 wherein R3 is selected from: C 1-2 alkyl, and Cl or a pharmaceutically acceptable salt thereof.

13. A compound according to claim 7 wherein R4 is —CH 3 , or a pharmaceutically acceptable salt thereof.

14. A compound according to claim 7 wherein R4 is H, or a pharmaceutically acceptable salt thereof.

15. A compound according to claim 6 wherein R5 is selected from: —CH 3 , and —NH 2 or a pharmaceutically acceptable salt thereof.

16. A compound according to claim 15 wherein R5 is —CH 3 or a pharmaceutically acceptable salt thereof.

17. A compound according to claim 1 wherein R6 is selected from: —CH 3 , —CH 2 OH, —CH 2 OCH 3 , —CH(OH)Me or a pharmaceutically acceptable salt thereof.

18. A compound according to claim 1 wherein R7 is H or a pharmaceutically acceptable salt thereof.

19. A compound which is:

or a pharmaceutically acceptable salt thereof.

20. A pharmaceutical composition comprising a compound according to claim 1 , and at least one of a pharmaceutically acceptable carrier, diluent, or excipient.

21. A pharmaceutical composition comprising a compound according to claim 19 and at least one of a pharmaceutically acceptable carrier, diluent, or excipient.

22. A method of treating a patient in need of treatment for cardiovascular disease, dyslipidemia, atherosclerosis, or hypertriglyceridemia, the method comprises administering to the patient an effective amount of a compound according to claim 1 .

23. A method of treating a patient in need of treatment for cardiovascular disease, dyslipidemia, atherosclerosis, or hypertriglyceridemia, the method comprises administering to the patient an effective amount of a composition according to claim 20 .

24. A method of treating a patient in need of treatment for cardiovascular disease, dyslipidemia, atherosclerosis, or hypertriglyceridemia, the method comprises administering to the patient an effective amount of a compound according to claim 19 .

25. A method of treating a patient in need of treatment for cardiovascular disease, dyslipidemia, atherosclerosis, or hypertriglyceridemia, the method comprises administering to the patient an effective amount of a composition according to claim 21 .

Assignees

• Lilly Co Eli

Inventors

• Escribano Ana Maria
• Gonzalez Maria Rosario
• Lafuente Blanco Celia
• Martin-Ortega Finger Maria Dolores
• Wiley Michael R

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title