Granted Patent B2

US 12,202,790 · App. 17/052,224 · Granted Jan 21, 2025

Inventors: Per Wikström (Färentuna, SE); Erik Walum (Stockholm, SE)

Assignee: GLUCOX BIOTECH AB

C07C311/16A61P9/10

Abstract

Claims (66)

1. A compound of formula (Ia)

or a pharmaceutically acceptable salt thereof, wherein

m is 1;

n is an integer of from 3 to 5;

each R 1 is independently selected from C1-C6 alkyl, C3-C6 carbocyclyl, C3-C6 carbocyclyl-C1-C3 alkyl, C1-C6 alkoxy, C1-C6 alkoxy-C1-C3 alkyl, C3-C6 carbocyclyloxy, C3-C6 carbocyclyloxy-C1-C3 alkyl, 4- to 6-membered heterocyclyl, 4- to 6-membered heterocyclyl-C1-C3 alkyl, hydroxy, hydroxy-C1-C3 alkyl, Cl, and Br; and when n is at least 4, two R 1 attached to adjacent atoms of the phenyl ring, together with the phenyl ring atoms to which they are attached, may form a 4- to 6-membered non-aromatic ring optionally containing one or more heteroatoms and optionally substituted with one or more moieties independently selected from C1-C3 alkyl and halogen;

one R 1a is halogen, and the other R 1a is selected from C1-C6 alkyl, C1-C6 alkoxy, hydroxy, and halogen;

R 2 is selected from C1-C3 alkyl, halogen, hydroxy, and hydroxy-C1-C3 alkyl;

R 3 , R 4 , R 5 , and R 6 are independently selected from H and F;

any alkyl is optionally substituted with one or more halogens; and

any carbocyclyl or heterocyclyl is optionally substituted with one or more moieties independently selected from halogen and C1-C3 alkyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from C1-C3 alkyl, halogen, and hydroxy.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from methyl, trifluoromethyl, F, CI, and hydroxy.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently selected from C1-C6 alkyl, C3-C6 cyclolalkyl, C3-C6 cycloalkyl-C1-C3 alkyl, C1-C6 alkoxy, C1-C6 alkoxy-C1-C3 alkyl, hydroxy, hydroxy-C1-C3 alkyl, Cl, and Br; and when n is at least 4, two R 1 attached to adjacent atoms of the phenyl ring, together with the phenyl ring atoms to which they are attached, may form a 4- to 6-membered non-aromatic ring optionally containing one or more heteroatoms and optionally substituted with one or more moieties independently selected from C1-C3 alkyl and halogen.

5. The compound of claim 1 , of formula (Ib)

or a pharmaceutically acceptable salt thereof, wherein

k is 1;

and

m, n, and each R 1 , R 1a , R 2 , R 3 , R 4 , R 5 , and R 6 are as defined in claim 1 .

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein one R 1a is halogen, and the other R 1a is independently selected from C1-C3 alkyl, hydroxy, and halogen.

7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein one R 1a is chloro, and the other R 1a is independently selected from methyl, hydroxy, and chloro.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 3.

9. A compound according to claim 1 , selected from

4-bromo-2,6-dichloro-N-[2-(2-fluorophenyl)ethyl]benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-[2-(2-methylphenyl)ethyl]benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-{2-[2-(trifluoromethyl)phenyl]ethyl}benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-[2-(2-chlorophenyl)ethyl]benzene-1-sulfonamide;

2,6-dichloro-N-[2-(2-fluorophenyl)ethyl]-4-(pyridin-3-yl) benzene-1-sulfonamide;

2,6-dichloro-4-cyclopropyl-N-[2-(2-fluorophenyl)ethyl]benzene-1-sulfonamide;

2,6-dichloro-N-[2-(2-chlorophenyl)ethyl]-4-cyclopropylbenzene-1-sulfonamide;

2,6-dichloro-N-[2-(2-chlorophenyl)ethyl]-4-(trifluoromethyl) benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-[2,2-difluoro-2-(2-methylphenyl)ethyl]benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-[2-(2-chlorophenyl)-2,2-difluoroethyl]benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-[2-fluoro-2-(2-methylphenyl)ethyl]benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-[2-(2-hydroxyphenyl)ethyl]benzenesulfonamide;

2,6-dichloro-N-[2-(2-hydroxyphenyl)ethyl]-4-(trifluoromethyl) benzenesulfonamide;

2,4-dichloro-6-hydroxy-N-[2-(2-hydroxyphenyl)ethyl]benzenesulfonamide;

2,4-dichloro-6-hydroxy-N-[2-(o-tolyl)ethyl]benzenesulfonamide; and

6-chloro-3-hydroxy-N-[2-(2-hydroxyphenyl)ethyl]-2,4-dimethyl-benzenesulfonamide;

or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising a compound as defined in claim 1

or a pharmaceutically acceptable salt thereof,

and optionally a pharmaceutically acceptable excipient.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is selected from C1-C6 alkyl, C3-C6 cyclolalkyl, C1-C6 alkoxy, hydroxy, Cl, and Br.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is selected from C1-C3 alkyl, Cl, and Br.

13. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein R 1 is Cl or Br.

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1a is Cl.

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from C1-C3 alkyl.

16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 and R 4 are H; and R 5 , and R 6 are independently selected from H and F.

17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each one of R 3 , R 4 , R 5 , and R 6 is H.

18. The pharmaceutical composition of claim 10 , wherein the compound is selected from

4-bromo-2,6-dichloro-N-[2-(2-fluorophenyl)ethyl]benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-[2-(2-methylphenyl)ethyl]benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-{2-[2-(trifluoromethyl)phenyl]ethyl}benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-[2-(2-chlorophenyl)ethyl]benzene-1-sulfonamide;

2,6-dichloro-N-[2-(2-fluorophenyl)ethyl]-4-(pyridin-3-yl) benzene-1-sulfonamide;

2,6-dichloro-4-cyclopropyl-N-[2-(2-fluorophenyl)ethyl]benzene-1-sulfonamide;

2,6-dichloro-N-[2-(2-chlorophenyl)ethyl]-4-cyclopropylbenzene-1-sulfonamide;

2,6-dichloro-N-[2-(2-chlorophenyl)ethyl]-4-(trifluoromethyl) benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-[2,2-difluoro-2-(2-methylphenyl)ethyl]benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-[2-(2-chlorophenyl)-2,2-difluoroethyl]benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-[2-fluoro-2-(2-methylphenyl)ethyl]benzene-1-sulfonamide;

4-bromo-2,6-dichloro-N-[2-(2-hydroxyphenyl)ethyl]benzenesulfonamide;

2,6-dichloro-N-[2-(2-hydroxyphenyl)ethyl]-4-(trifluoromethyl) benzenesulfonamide;

2,4-dichloro-6-hydroxy-N-[2-(2-hydroxyphenyl)ethyl]benzenesulfonamide;

2,4-dichloro-6-hydroxy-N-[2-(o-tolyl)ethyl]benzenesulfonamide; and

6-chloro-3-hydroxy-N-[2-(2-hydroxyphenyl)ethyl]-2,4-dimethyl-benzenesulfonamide.

Assignments (1)

Priority Claims (1)

Continuity (1)

References Cited (142)