Saturated-ring-fused dihydropyrimidinone or dihydrotriazinone compounds and pharmaceutical use thereof
The present invention relates to saturated-ring-fused dihydropyrimidinone or dihydrotriazinone compounds, or pharmaceutically acceptable salts having RORγ antagonist activity, pharmaceutical compositions comprising the same, and pharmaceutical use thereof. A compound of Formula [I] or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the same, and pharmaceutical use thereof are provided: wherein each substituent is defined as defined in the description.
1. A compound of Formula [I]:
wherein R 1 is
(1) C 1-8 alkyl,
(2) halo-C 1-8 alkyl,
(3) C 3-8 cycloalkyl optionally substituted with the same or different 1 to 3 substituents selected from Group A 1 , or
(4) C 3-8 cycloalkyl-C 1-4 alkyl wherein the C 3-8 cycloalkyl moiety may be optionally substituted with the same or different 1 to 3 substituents selected from Group A 1 ,
Group A 1 is
(1) halogen,
(2) C 1-4 alkyl, or
(3) halo-C 1-4 alkyl,
X 1 is
(1) a bond, or
(2) —O—,
R 2 is
(1) hydrogen, or
(2) halogen,
R 3 is
(1) hydrogen, or
(2) —Y 3 —COO—R 30 ,
Y 3 is
(1) C 1-8 alkylene,
(2) C 3-8 cycloalkylene,
(3) bridged C 5-8 cycloalkylene, or
(4) C 6-14 arylene,
R 30 is
(1) hydrogen, or
(2) C 1-4 alkyl,
X 2 is
(1) ═C(R 4 )—, or
(2) ═N—,
R 4 is
(1) hydrogen, or
(2) C 1-4 alkyl,
X 3 is
(1) —C(R 5 )(R 6 )—,
X 4 is
(1) a bond, or
(2) —C(R 7 )(R 8 )—,
X 5 is
(1) —C(R 9 )(R 10 )—,
(2) —N(R 11 )—, or
(3) —O—,
R 5 and R 6 are each independently
(1) hydrogen,
(2) C 1-4 alkyl,
(3) halo-C 1-4 alkyl,
(4) cyano-C 14 alkyl, or
(5) C 1-4 alkyl substituted with one substituent selected from the group consisting of —O—R 51 , —CO—R 61 , —COO—R 52 , —N(R 71 )(R 72 ), —CO—N(R 73 )(R 74 ), —N(R 75 )—CO—R 62 , —N(R 76 )—COO—R 53 , and —O—S(O) 2 —R 63 ,
R 7 , R 8 , R 9 , and R 10 are each independently
(1) hydrogen,
(2) halogen,
(3) cyano,
(4) hydroxy,
(5) C 1-4 alkyl,
(6) halo-C 1-4 alkyl,
(7) cyano-C 1-4 alkyl,
(8) C 1-4 alkoxy, or
(9) C 1-4 alkyl substituted with one substituent selected from the group consisting of —O—R 51 , —CO—R 61 , —COO—R 52 , —N(R 71 )(R 72 ), —CO—N(R 73 )(R 74 ), —N(R 75 )—CO—R 62 , —N(R 76 )—COO—R 53 , and —O—S(O) 2 —R 63 ,
R 51 , R 52 , and R 53 are each independently
(1) hydrogen,
(2) C 1-4 alkyl, or
(3) C 6-14 aryl-C 14 alkyl,
R 61 , R 62 , and R 63 are each independently
(1) C 1-4 alkyl,
R 71 , R 72 , R 73 , R 74 , R 75 , and R 76 are each independently
(1) hydrogen, or
(2) C 1-4 alkyl,
R 11 is
(1) —CO—R 111 , or
(2) —COO—R 112 ,
R 111 is
(1) C 1-4 alkyl, and
R 112 is
(1) C 1-4 alkyl, or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , having a structure of Formula [II]:
wherein each variable is defined as defined in claim 1 , or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 1 , wherein X 2 is ═N—, or a pharmaceutically acceptable salt thereof.
4. The compound according to claim 1 , wherein X 2 is ═C(R 4 )— and R 4 is hydrogen, or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 1 , wherein R 3 is hydrogen, or a pharmaceutically acceptable salt thereof.
6. The compound according to claim 1 , wherein R 3 is —Y 3 —COO—R 30 ,
Y 3 is
(1) C 1-8 alkylene,
(2) C 3-8 cycloalkylene, or
(3) bridged C 5-8 cycloalkylene, and
R 30 is hydrogen or C 1-4 alkyl, or a pharmaceutically acceptable salt thereof.
7. The compound according to claim 1 , wherein R 2 is halogen, or a pharmaceutically acceptable salt thereof.
8. The compound according to claim 1 , wherein R 1 is C 1-8 alkyl and X 1 is a bond, or a pharmaceutically acceptable salt thereof.
9. The compound according to claim 1 , wherein R 5 and R 6 are each independently hydrogen or C 1-4 alkyl, or a pharmaceutically acceptable salt thereof.
10. The compound according to claim 1 , wherein X 4 is a bond or —C(R 7 )(R 8 )— and both of R 7 and R 8 are hydrogen, or a pharmaceutically acceptable salt thereof.
11. The compound according to claim 1 , wherein X 5 is —C(R 9 )(R 10 )— or —O— and both of R 9 and R 10 are hydrogen, or a pharmaceutically acceptable salt thereof.
12. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
13. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
14. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
15. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
16. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
17. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
18. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
19. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
20. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
21. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
22. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
23. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
24. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
25. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
26. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
27. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.
28. The compound according to claim 1 , having a structure:
or a pharmaceutically acceptable salt thereof.