IP Library › Granted Patent US 10,227,338
Granted Patent B2
US 10,227,338 · App. 15/771,775 · Granted Mar 12, 2019

Substituted benzenesulfonamides as sodium channel blockers

Inventors: Hyung-Geun Lee (Gyeonggi-do, KR); Il-Hwan Kim (Chungcheongbuk-do, KR); Myunggi Jung (Gyeonggi-do, KR); Hyo Shin Kim (Incheon, KR); Chun Ho Lee (Seoul, KR); Sun Ah Jun (Gyeonggi-do, KR); Ji Sung Yoon (Gyeonggi-do, KR); Sung-Young Kim (Gyeonggi-do, KR)
Assignee: Daewoong Pharmaceutical Co., Ltd.
C07D417/12A61K31/427A61K31/497C07D277/52C07D417/14
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 10,227,338
App. No.
15/771,775
Granted
Mar 12, 2019
Kind
B2
Abstract

The invention relates to a compound represented by Chemical Formula 1, below, a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the compound or salt. The compound of the invention or pharmaceutically acceptable salts thereof can be used for the prevention or treatment of sodium channel blocker-related diseases. in Chemical Formula 1, R 1 is hydrogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, halogen, or cyano, R 2 and R 3 are each independently hydrogen, or halogen, R 4 is C 5-10 heteroaryl containing one or two elements each independently selected from the group consisting of N, S and O, wherein the C 5-10 heteroaryl is unsubstituted or substituted with C 1-4 alkyl or halogen, R 5 is —CH 2 CH 2 —N(R 7 )(R 8 ), or —CH 2 CH 2 CH 2 —N(R 7 )(R 8 ), R 6 is hydrogen, or C 1-4 alkyl; or R 5 and R 6 together form C 3-5 alkylene, (C 2-4 alkylene)-N(R 9 )—(C 2-4 alkylene), or (C 2-4 alkylene)-O—(C 2-4 alkylene), wherein the C 3-5 alkylene, or C 2-4 alkylene is each independently unsubstituted or substituted with one or two R 10 , R 7 , R 8 , and R 9 are each independently hydrogen, or C 1-4 alkyl, R 10 is C 1-4 alkyl, C 1-4 alkoxy, halogen, amino, NH(C 1-4 alkyl), N(C 1-4 alkyl) 2 , NHCO(C 1-4 alkyl), or pyrrolidinyl, X 1 is C—R′, or N, wherein R′ is hydrogen, or halogen, X 2 is CH, or N, and X 3 is N—R″, wherein R″ is hydrogen, or C 1-4 alkyl.

Claims (220)

1. A compound represented by Chemical Formula 1:

or a pharmaceutically acceptable salt thereof,

wherein:

R 1 is hydrogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, halogen or cyano;

R 2 is hydrogen or halogen;

R 3 is hydrogen or halogen;

R 4 is C 2-10 heteroaryl, wherein the C 2-10 heteroaryl contains 1 or 2 heteroatoms independently selected from the group consisting of nitrogen, sulfur and oxygen and further wherein the C 2-10 heteroaryl is optionally substituted with C 1-4 alkyl or halogen;

R 5 is —(CH 2 ) 2 N(R 7 )(R 8 ) or —(CH 2 ) 3 N(R 7 )(R 8 );

R 6 is hydrogen or C 1-4 alkyl; or

R 5 and R 6 , together form C 3-5 alkylene, (C 2-4 alkylene)-N(R 9 )—(C 2-4 alkylene) or (C 2-4 alkylene)-O—(C 2-4 alkylene), wherein the C 3-5 alkylene or each C 2-4 alkylene is independently and optionally substituted with 1 or 2 R 10 ;

R 7 is hydrogen or C 1-4 alkyl;

R 8 is hydrogen or C 1-4 alkyl;

R 9 is hydrogen or C 1-4 alkyl;

R 10 is C 1-4 alkyl, C 1-4 alkoxy, halogen, NH 2 , NH(C 1-4 alkyl), N(C 1-4 alkyl) 2 , NHCO(C 1-4 alkyl) or pyrrolidinyl;

R′ is hydrogen or halogen;

R″ is hydrogen or C 1-4 alkyl;

X 1 is CR′ or N;

X 2 is CH or N; and

X 3 is NR″.

2. The compound according to claim 1 , wherein the compound is represented by Chemical Formula 1′:

or a pharmaceutically acceptable salt thereof,

wherein:

n is 1, 2, 3 or 4;

R 11 is hydrogen or C 1-4 alkyl;

R 12 is hydrogen C 1-4 alkyl, C 1-4 alkoxy, halogen, NH 2 , NH(C 1-4 alkyl), N(C 1-4 alkyl) 2 , NHCO(C 1-4 alkyl) or pyrrolidinyl; and

X 4 is a bond, NH, N(C 1-4 alkyl) or O.

3. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 is hydrogen, methyl, methoxy, trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoro, chloro or cyano.

4. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein:

R 2 is hydrogen, fluoro or chloro; and

R 3 is hydrogen, fluoro or chloro.

5. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein:

R 4 is thiadiazolyl, thiazolyl, isoxazolyl, oxazolyl, pyrazolyl, pyridinyl, pyrimidinyl or pyrazinyl, each optionally substituted.

6. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein:

X 1 is CH, CF or N; and

X 2 is CH or N;

provided that both X 1 and X 2 are not N.

7. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein:

X 3 is NH.

8. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 is hydrogen, methyl, methoxy, trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoro, chloro or cyano.

9. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 2 is hydrogen, fluoro or chloro; and

R 3 is hydrogen, fluoro or chloro.

10. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 4 is thiadiazolyl, thiazolyl, isoxazolyl, oxazolyl, pyrazolyl, pyridinyl, pyrimidinyl or pyrazinyl, each optionally substituted.

11. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 5 is —(CH 2 ) 2 N(H)(CH 3 ), —(CH 2 ) 2 N(CH 3 ) 2 or —(CH 2 ) 3 N(H)(CH 3 ); and

R 6 is hydrogen or methyl.

12. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 5 and R 6 , together form C 3-5 alkylene, (C 2-4 alkylene)-N(R 9 )—(C 2-4 alkylene) or (C 2-4 alkylene)-O—(C 2-4 alkylene), wherein the C 3-5 alkylene or each C 2-4 alkylene is independently and optionally substituted with 1 or 2 methyl, methoxy, fluoro, NH 2 , NH(CH 3 ), N(CH 3 ) 2 , N(CH 2 CH 3 ) 2 , NHCO(CH 3 ) or pyrrolidinyl.

13. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 5 and R 6 , together with the nitrogen atom to which they are attached, form a heterocyclic ring selected from the group consisting of:

14. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

X 1 is CH, CF or N; and

X 2 is CH or N;

provided that both X 1 and X 2 are not N.

15. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

X 3 is NH.

16. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

1) 5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

2) 5-chloro-4-((4-chloro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

3) (R)-5-chloro-4-((4-chloro-2-(2-methylpiperazin-1-yl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

4) (R)-5-chloro-4-((4-chloro-2-(3-(methylamino)piperidin-1-yl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

5) (R)—N-(1-(5-chloro-2-((2-chloro-5-fluoro-4-(N-(thiazol-4-yl)sulfamoyl)phenyl)amino)phenyl)pyrrolidin-3-yl)acetamide,

6) 5-chloro-4-((4-chloro-2-(3-(diethylamino)pyrrolidin-1-yl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

7) 4-((2-([1,3′-bipyrrolidin]-1′-yl)-4-chlorophenyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

8) 5-chloro-2-fluoro-4-((4-methyl-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

9) (S)-5-chloro-4-((4-chloro-2-(3-methylpiperazin-1-yl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

10) 4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

11) 3-chloro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

12) 3,5-difluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

13) 2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

14) 4-((2-(3-(methylamino)pyrrolidin-1-yl)-4-(trifluoromethoxy)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

15) 3,5-difluoro-4-((2-(3-(methylamino)pyrrolidin-1-yl)-4-(trifluoromethoxy)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

16) 2-fluoro-4-((2-(3-(methylamino)pyrrolidin-1-yl)-4-(trifluoromethoxy)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

17) 5-chloro-2-fluoro-4-((2-(3-(methylamino)pyrrolidin-1-yl)-4-(trifluoromethoxy)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

18) 5-chloro-4-((5-chloro-3-(3-(methylamino)pyrrolidin-1-yl)pyridin-2-yl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

19) 5-chloro-4-((6-chloro-2-(3-(methylamino)pyrrolidin-1-yl)pyridin-3-yl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

20) 5-chloro-2-fluoro-4-((2-(3-(methylamino)pyrrolidin-1-yl)-4-(trifluoromethyl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

21) 5-chloro-4-((4-(difluoromethoxy)-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

22) (R)-4-((4-fluoro-2-(3-(methylamino)piperidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

23) (R)-2-fluoro-4-((4-fluoro-2-(3-(methylamino)piperidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

24) (R)-3-chloro-4-((4-fluoro-2-(3-(methylamino)piperidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

25) (R)-3,5-difluoro-4-((4-fluoro-2-(3-(methylamino)piperidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

26) (R)-5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)piperidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

27) (R)-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

28) (R)-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

29) (R)-3-chloro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

30) (R)-3,5-difluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

31) (R)-5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

32) 5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

33) 4-((2-(3-aminopyrrolidin-1-yl)-4-fluorophenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

34) 4-((2-(3-aminopyrrolidin-1-yl)-4-fluorophenyl)amino)-3-chloro-N-(thiazol-4-yl)benzenesulfonamide,

35) 4-((2-(3-aminopyrrolidin-1-yl)-4-fluorophenyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

36) 4-((2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

37) 2-fluoro-4-((2-(3-(methylamino)pyrrolidin-1-yl)-4-(trifluoromethyl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

38) 3-chloro-4-((2-(3-(methylamino)pyrrolidin-1-yl)-4-(trifluoromethyl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

39) 4-((4-(difluoromethoxy)-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

40) 3-chloro-4-((4-(difluoromethoxy)-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

41) (R)-4-((4-fluoro-2-(3-fluoropyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

42) (R)-2-fluoro-4-((4-fluoro-2-(3-fluoropyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

43) (R)-3-chloro-4-((4-fluoro-2-(3-fluoropyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

44) (R)-3,5-difluoro-4-((4-fluoro-2-(3-fluoropyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

45) (R)-5-chloro-2-fluoro-4-((4-fluoro-2-(3-fluoropyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

46) 2-fluoro-4-((3-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

47) 3-chloro-4-((3-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

48) 5-chloro-2-fluoro-4-((3-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

49) 2-fluoro-4-((2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

50) 3-chloro-4-((2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

51) 3,5-difluoro-4-((2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

52) 5-chloro-2-fluoro-4-((2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

53) 2-fluoro-4-((4-methoxy-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

54) 3-chloro-4-((4-methoxy-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

55) 5-chloro-2-fluoro-4-((4-methoxy-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

56) (R)-4-((4-methoxy-2-(3-(methylamino)piperidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

57) (R)-2-fluoro-4-((4-methoxy-2-(3-(methylamino)piperidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

58) (R)-3-chloro-4-((4-methoxy-2-(3-(methylamino)piperidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

59) (R)-3,5-difluoro-4-((4-methoxy-2-(3-(methylamino)piperidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

60) (R)-5-chloro-2-fluoro-4-((4-methoxy-2-(3-(methylamino)piperidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

61) 3-chloro-4-((4-fluoro-2-(4-methylpiperazin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

62) 5-chloro-2-fluoro-4-((4-fluoro-2-(4-methylpiperazin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

63) (S)-5-chloro-4-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-fluorophenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

64) (S)-5-chloro-4-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-(trifluoromethyl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

65) 5-chloro-2-fluoro-4-((2-(4-methylpiperazin-1-yl)-4-(trifluoromethyl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

66) 5-chloro-4-((4-(difluoromethoxy)-2-(4-methylpiperazin-1-yl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

67) 5-chloro-2-fluoro-4-((2-(4-methylpiperazin-1-yl)-4-(trifluoromethoxy)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

68) (S)-3-chloro-4-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-(trifluoromethyl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

69) (S)-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

70) (S)-5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

71) (S)-5-chloro-4-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxyphenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

72) (S)-5-chloro-4-((4-(difluoromethoxy)-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

73) (R)-5-chloro-4-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-fluorophenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

74) (R)-5-chloro-4-((2-(3-(dimethylamino)pyrrolidin-1-yl)-4-(trifluoromethyl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

75) (R)-5-chloro-4-((4-(difluoromethoxy)-2-(3-(dimethylamino)pyrrolidin-1-yl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

76) 4-((2-(1,4-diazepan-1-yl)-4-fluorophenyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

77) 5-chloro-4-((4-cyano-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

78) (R)—N-(1-(2-((2-chloro-5-fluoro-4-(N-(thiazol-4-yl)sulfamoyl)phenyl)amino)-5-(trifluoromethyl)phenyl)pyrrolidin-3-yl)acetamide,

79) (R)—N-(1-(2-((2-chloro-4-(N-(thiazol-4-yl)sulfamoyl)phenyl)amino)-5-(trifluoromethyl)phenyl)pyrrolidin-3-yl)acetamide,

80) (S)-3-chloro-4-((2-(3-(methylamino)pyrrolidin-1-yl)-4-(trifluoromethyl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

81) (S)-5-chloro-2-fluoro-4-((2-(3-(methylamino)pyrrolidin-1-yl)-4-(trifluoromethyl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

82) 5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)azetidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

83) 4-((2-(3-aminoazetidin-1-yl)-4-fluorophenyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

84) 5-chloro-4-((2-(3-(dimethylamino)azetidin-1-yl)-4-fluorophenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

85) N-(1-(2-((2-chloro-5-fluoro-4-(N-(thiazol-4-yl)sulfamoyl)phenyl)amino)-5-fluorophenyl)azetidin-3-yl)acetamide,

86) 5-chloro-2-fluoro-4-((4-fluoro-2-(3-methoxypyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

87) 5-chloro-2-fluoro-4-((2-(3-methoxypyrrolidin-1-yl)-4-(trifluoromethyl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

88) (R)—N-(1-(2-((2-chloro-5-fluoro-4-(N-(thiazol-4-yl)sulfamoyl)phenyl)amino)-5-fluorophenyl)pyrrolidin-3-yl)acetamide,

89) 3-chloro-4-((4-fluoro-2-(3-methoxypyrrolidin-1-yl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

90) 3-chloro-4-((2-(3-methoxypyrrolidin-1-yl)-4-(trifluoromethyl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

91) (R)—N-(1-(2-((2-chloro-4-(N-(thiazol-4-yl)sulfamoyl)phenyl)amino)-5-fluorophenyl)pyrrolidin-3-yl)acetamide,

92) 5-chloro-2-fluoro-4-((4-fluoro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

93) 3-chloro-4-((2-((2-(dimethylamino)ethyl)(methyl)amino)-4-fluorophenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

94) 5-chloro-4-((2-((2-(dimethylamino)ethyl)(methyl)amino)-4-fluorophenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

95) 5-chloro-2-fluoro-4-((2-(methyl(2-(methylamino)ethyl)amino)-4-(trifluoromethyl)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

96) 5-chloro-2-fluoro-4-((4-fluoro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(5-fluoropyrimidin-2-yl)benzenesulfonamide,

97) 5-chloro-2-fluoro-N-(5-fluoropyrimidin-2-yl)-4-((2-(methyl(2-(methylamino)ethyl)amino)-4-(trifluoromethyl)phenyl)amino)benzenesulfonamide,

98) 5-chloro-4-((4-(difluoromethoxy)-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

99) 5-chloro-4-((4-cyano-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

100) 5-chloro-4-((4-cyano-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(5-fluoropyrimidin-2-yl)benzenesulfonamide,

101) 5-chloro-4-((4-(difluoromethoxy)-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(5-fluoropyrimidin-2-yl)benzenesulfonamide,

102) 5-chloro-2-fluoro-N-(5-fluoropyrimidin-2-yl)-4-((2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)benzenesulfonamide,

103) 5-chloro-2-fluoro-4-((4-fluoro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(5-fluoropyridin-2-yl)benzenesulfonamide,

104) 5-chloro-2-fluoro-4-((4-fluoro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(pyridin-2-yl)benzenesulfonamide,

105) 5-chloro-2-fluoro-4-((4-fluoro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(thiazol-2-yl)benzenesulfonamide,

106) 5-chloro-4-((4-cyano-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(5-fluoropyridin-2-yl)benzenesulfonamide,

107) 5-chloro-4-((4-cyano-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(pyridin-2-yl)benzenesulfonamide,

108) 5-chloro-4-((4-cyano-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide,

109) 5-chloro-2-fluoro-N-(5-fluoropyridin-2-yl)-4-((2-(methyl(2-(methylamino)ethyl)amino)-4-(trifluoromethyl)phenyl)amino)benzenesulfonamide,

110) 5-chloro-2-fluoro-4-((2-(methyl(2-(methylamino)ethyl)amino)-4-(trifluoromethyl)phenyl)amino)-N-(pyridin-2-yl)benzenesulfonamide,

111) 5-chloro-2-fluoro-4-((2-(methyl(2-(methylamino)ethyl)amino)-4-(trifluoromethyl)phenyl)amino)-N-(thiazol-2-yl)benzenesulfonamide,

112) 5-chloro-2-fluoro-N-(5-fluoropyridin-2-yl)-4-((2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)benzenesulfonamide,

113) 5-chloro-2-fluoro-4-((2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(pyridin-2-yl)benzenesulfonamide,

114) 5-chloro-2-fluoro-4-((2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(thiazol-2-yl)benzenesulfonamide,

115) 5-chloro-4-((4-(difluoromethoxy)-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(5-fluoropyridin-2-yl)benzenesulfonamide,

116) 5-chloro-4-((4-(difluoromethoxy)-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide,

117) 5-chloro-4-((4-(difluoromethoxy)-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(pyridin-2-yl)benzenesulfonamide,

118) 5-chloro-2-fluoro-N-(5-fluoropyridin-2-yl)-4-((4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)benzenesulfonamide,

119) 5-chloro-2-fluoro-4-((4-meth oxy-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(thiazol-2-yl)benzenesulfonamide,

120) 5-chloro-2-fluoro-4-((4-meth oxy-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

121) 5-chloro-2-fluoro-4-((2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

122) 5-chloro-2-fluoro-N-(5-fluoropyrimidin-2-yl)-4-((4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)benzenesulfonamide,

123) 5-chloro-4-((4-chloro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide,

124) 5-chloro-4-((4-chloro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(5-fluoropyrimidin-2-yl)benzenesulfonamide,

125) 5-chloro-4-((4-chloro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(5-fluoropyridin-2-yl)benzenesulfonamide,

126) 5-chloro-4-((4-chloro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide,

127) 5-chloro-N-(5-chlorothiazol-2-yl)-2-fluoro-4-((4-fluoro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)benzenesulfonamide,

128) 5-chloro-2-fluoro-4-((4-fluoro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(5-fluorothiazol-2-yl)benzenesulfonamide,

129) 5-chloro-N-(5-chlorothiazol-2-yl)-2-fluoro-4-((2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)benzenesulfonamide,

130) 5-chloro-N-(5-chlorothiazol-2-yl)-2-fluoro-4-((4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)benzenesulfonamide,

131) 5-chloro-2-fluoro-N-(5-fluorothiazol-2-yl)-4-((2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)benzenesulfonamide,

132) 5-chloro-2-fluoro-N-(5-fluorothiazol-2-yl)-4-((4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)benzenesulfonamide,

133) 5-chloro-2-fluoro-4-((4-fluoro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide,

134) 5-chloro-2-fluoro-4-((2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide,

135) 5-chloro-2-fluoro-4-((4-fluoro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(5-methyl-1H-pyrazol-3-yl)benzenesulfonamide,

136) 5-chloro-2-fluoro-4-((2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(5-methyl-1H-pyrazol-3-yl)benzenesulfonamide,

137) 5-chloro-4-((2-((2-(dimethylamino)ethyl)(methyl)amino)-4-fluorophenyl)amino)-2-fluoro-N-(5-fluoropyridin-2-yl)benzenesulfonamide,

138) 5-chloro-4-((2-((2-(dimethylamino)ethyl)(methyl)amino)-4-fluorophenyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide,

139) 5-chloro-N-(5-chlorothiazol-2-yl)-4-((2-((2-(dimethylamino)ethyl)(methyl)amino)-4-fluorophenyl)amino)-2-fluorobenzenesulfonamide,

140) 5-chloro-N-(5-chlorothiazol-2-yl)-4-((2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)amino)-2-fluorobenzenesulfonamide,

141) 5-chloro-2-fluoro-4-((4-fluoro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(5-methylthiazol-2-yl)benzenesulfonamide,

142) 5-chloro-2-fluoro-4-((4-fluoro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)-N-(oxazol-2-yl)benzenesulfonamide,

143) N-(5-(tert-butyl)isoxazol-3-yl)-5-chloro-2-fluoro-4-((4-fluoro-2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)benzenesulfonamide,

144) N-(5-(tert-butyl)isoxazol-3-yl)-5-chloro-2-fluoro-4-((2-(methyl(2-(methylamino)ethyl)amino)phenyl)amino)benzenesulfonamide,

145) 5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide,

146) 5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(1-methyl-1H-pyrazol-3-yl)benzenesulfonamide,

147) 5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(pyrimidin-4-yl)benzenesulfonamide,

148) 5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(5-fluoropyrimidin-2-yl)benzenesulfonamide,

149) 5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(pyrazin-2-yl)benzenesulfonamide,

150) 5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide,

151) 5-chloro-2-fluoro-4-((4-fluoro-2-(3-(methylamino)pyrrolidin-1-yl)phenyl)amino)-N-(pyrimidin-5-yl)benzenesulfonamide,

152) 5-chloro-2-fluoro-4-((4-fluoro-2-((2-(methylamino)ethyl)amino)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide,

153) 5-chloro-4-((2-((2-(dimethylamino)ethyl)amino)-4-fluorophenyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide, and

154) 5-chloro-2-fluoro-4-((4-fluoro-2-(methyl(3-(methylamino)propyl)amino)phenyl)amino)-N-(thiazol-4-yl)benzenesulfonamide.

17. A pharmaceutical composition comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, as an active ingredient and a pharmaceutically acceptable carrier.

18. A method for inhibiting a voltage-gated sodium channel in a patient, comprising administering to the patient in need thereof a pharmaceutical composition according to claim 17 .

19. The method according to claim 18 , wherein the patient has a sodium channel blocker-related disease.

20. The method according to claim 19 , wherein the sodium channel blocker-related disease is a neuropathic disease.

21. The method according to claim 19 , wherein the sodium channel blocker-related disease is selected from the group consisting of acute pain, chronic pain, neuropathic pain, postoperative pain, visceral pain, nerve damage, migraine, epilepsy, depression, anthralgia, erythralgia, arrhythmia, myotonia, ataxia, neuropathy, multiple sclerosis, irritable bowel syndrome, urinary incontinence and paroxysmal extreme pain disorder.

22. The method according to claim 21 , wherein the neuropathy is diabetic neuropathy.

Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME PREVIOUSLY RECORDED ON REEL 56854 FRAME 612. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Apr 7, 2026
From: DAEWOONG PHARMACEUTICAL CO., LTD.
To: IN THERAPEUTICS, CO. LTD.
Reel/Frame 075336/0433 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 14, 2021
From: DAEWOONG PHARMACEUTICAL CO., LTD.
To: IN THERAPEUTICS
Reel/Frame 056854/0612 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 2, 2018
From: LEE, HYUNG-GEUN; KIM, IL-HWAN; JUNG, MYUNGGI; KIM, HYO SHIN; LEE, CHUN HO; JUN, SUN AH; YOON, JI SUNG; KIM, SUNG-YOUNG
To: DAEWOONG PHARMACEUTICAL CO., LTD.
Reel/Frame 045690/0157 →
Priority Claims (1)
KR 10-2015-0159637 · Nov 13, 2015 · national
Continuity (1)
Related Publication 20180346459A1 · Dec 6, 2018