Cyclohexyl sulfonamide derivatives

Abstract

The present invention relates to compounds of formula I

Description

Claims

1. A compound of formula I:

2. The compound according to claim 1, wherein R3 is lower alkyl.

3. The compound according to claim 1, wherein R3 is C3-C8-alkyl.

4. The compound according to claim 1, wherein R3 is selected from the group consisting of —(CH2)m-aryl, wherein m is 0, 1 or 2 and wherein the aryl ring is unsubstituted or substituted with one, two or three groups independently selected from lower alkyl, halogen, lower halogenalkyl, cyano, lower cyanoalkyl, lower alkoxy, lower alkanoyl, benzoyl, lower halogenalkoxy, lower hydroxyalkyl, lower alkanoylamino and lower alkylsulfonyl, and —(CH2)n-heteroaryl, wherein n is 0, 1 or 2 and wherein the heteroaryl ring is unsubstituted or substituted with one, two or three groups independently selected from lower alkyl, halogen, lower halogenalkyl, cyano, lower cyanoalkyl, lower alkoxy, lower alkanoyl, benzoyl, lower halogenalkoxy, lower hydroxyalkyl, lower alkanoylamino and lower alkylsulfonyl.

5. The compound according to claim 1, wherein R3 is —(CH2)m-aryl, wherein m is 0, 1 or 2 and wherein the aryl ring is phenyl unsubstituted or substituted with one, two or three groups independently selected from lower alkyl, halogen, lower halogenalkyl, cyano, lower cyanoalkyl, lower alkoxy, lower alkanoyl, benzoyl, lower halogenalkoxy, lower hydroxyalkyl, lower alkanoylamino and lower alkylsulfonyl.

6. The compound according to claim 1, wherein R3 is phenyl substituted with one, two or three groups independently selected from lower alkyl, halogen, lower halogenalkyl, cyano, lower cyanoalkyl, lower alkoxy, lower alkanoyl, benzoyl, lower halogenalkoxy, lower hydroxyalkyl, lower alkanoylamino and lower alkylsulfonyl.

7. The compound according to claim 1, wherein R3 is —(CH2)n-heteroaryl, wherein n is 0, 1 or 2 and wherein the heteroaryl ring is unsubstituted or substituted with one or two groups independently selected from lower alkyl, halogen, lower halogenalkyl, cyano, lower cyanoalkyl, lower alkoxy, lower alkanoyl, benzoyl, lower halogenalkoxy, lower hydroxyalkyl, lower alkanoylamino and lower alkylsulfonyl.

8. The compound according to claim 1, wherein R3 is —(CH2)n-heteroaryl, wherein n is 0, 1 or 2 and heteroaryl is selected from the group consisting of pyridyl, thienyl, imidazolyl, isoxazolyl, thiazolyl and pyrazolyl, said heteroaryl ring being unsubstituted or substituted with one, two or three groups independently selected from lower alkyl, halogen, lower halogenalkyl, cyano, lower cyanoalkyl, lower alkoxy, lower alkanoyl, benzoyl, lower halogenalkoxy, lower hydroxyalkyl, lower alkanoylamino and lower alkylsulfonyl.

9. The compound according to claim 1, wherein R3 is pyridyl unsubstituted or substituted with halogen.

10. The compound according to claim 1, wherein R3 is —NR4R5 and R4 and R5 are lower alkyl.

11. The compound according to claim 1, wherein R1 is lower alkyl or cycloalkyl.

12. The compound according to claim 1, wherein R1 is lower alkyl.

13. The compound according to claim 1, wherein R1 is isopropyl or tert-butyl.

14. The compound according to claim 1, wherein R1 is cycloalkyl.

15. The compound according to claim 1, wherein R2 is selected from the group consisting of hydrogen, lower alkyl and lower cycloalkylalkyl.

16. The compound according to claim 1, wherein R2 is hydrogen.

17. The compound according to claim 1, wherein R2 is lower alkyl.

18. The compound according to claim 1, wherein R2 is lower cycloalkylalkyl.

19. The compound according to claim 1, selected from the group consisting of N-{trans-4-[(4-isopropylpiperazin-1-yl)carbonyl]cyclohexyl}-2-methylbenzene-sulfonamide,4-cyano-N-{trans-4-[(4-isopropylpiperazin-1-yl)carbonyl]cyclohexyl}benzene-sulfonamide,4-fluoro-N-{trans-4-[(4-isopropylpiperazin-1-yl)carbonyl]cyclohexyl}-2-methylbenzene-sulfonamide,1-(3-fluorophenyl)-N-{trans-4-[(4-isopropylpiperazin-1-yl)carbonyl]cyclohexyl}-methanesulfonamide,N-{trans-4-[(4-isopropylpiperazin-1-yl)carbonyl]cyclohexyl}-2,4,6-trimethylbenzene-sulfonamide,2,4-dichloro-N-{trans-4-[(4-isopropylpiperazin-1-yl)carbonyl]cyclohexyl}benzene-sulfonamide,2-chloro-N-{trans-4-[(4-isopropylpiperazin-1-yl)carbonyl]cyclohexyl}benzene-sulfonamide,3-chloro-4-fluoro-N-isopropyl-N-[trans-4-(4-isopropyl-piperazine-1-carbonyl)-cyclohexyl]-benzenesulfonamide,N-cyclopropylmethyl-N-[trans-4-(4-isopropyl-piperazine-1-carbonyl)-cyclohexyl]-2-methyl-benzenesulfonamide,N-cyclopropylmethyl-N-[trans-4-(4-isopropyl-piperazine-1-carbonyl)-cyclohexyl]-4-methoxy-benzenesulfonamide,N-cyclopropylmethyl-N-[trans-4-(4-isopropyl-piperazine-1-carbonyl)-cyclohexyl]-2,4,6-trimethyl-benzenesulfonamide,N-cyclopropylmethyl-N-[trans-4-(4-isopropyl-piperazine-1-carbonyl)-cyclohexyl]-4-trifluoromethoxy-benzenesulfonamide,trans-N-[4-(4-cyclopentyl-piperazine-1-carbonyl)-cyclohexyl]-2-methyl-benzenesulfonamide,trans-4-cyano-N-[4-(4-cyclopentyl-piperazine-1-carbonyl)-cyclohexyl]-benzenesulfonamide,trans-4-cyano-N-[4-(4-cyclobutyl-piperazine-1-carbonyl)-cyclohexyl]-benzenesulfonamide,trans-3-bromo-5-chloro-thiophene-2-sulfonic acid[4-(4-isopropyl-piperazine-1-carbonyl)-cyclohexyl]-amide,trans-3-bromo-5-chloro-thiophene-2-sulfonic acid[4-(4-cyclobutyl-piperazine-1-carbonyl)-cyclohexyl]-amide,trans-N-[4-(4-isopropyl-piperazine-1-carbonyl)-cyclohexyl]-2,4,6-trimethyl-N-(2,2,2-trifluoro-ethyl)-benzenesulfonamide,trans-N-[4-(4-isopropyl-piperazine-1-carbonyl)-cyclohexyl]-N-(2-methoxy-ethyl)-2,4,6-trimethyl-benzenesulfonamide,and pharmaceutically acceptable salts thereof.

20. A process for the manufacture of a compound according to claim 1, comprising the steps of: reacting a compound of formula II

21. A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 1 as well as a pharmaceutically acceptable carrier and/or adjuvant.

22. A method for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors, comprising the step of administering a therapeutically active amount of a compound according to claim 1 to a human being or animal in need thereof.

23. A method for the treatment or prevention of obesity in a human being or animal, comprising the step of administering to said human being or animal in need thereof a therapeutically effective amount of a compound according to claim 1 in combination or association with a therapeutically effective amount of a compound selected from the group consisting of a lipase inhibitor, an anorectic agent, a selective serotonin reuptake inhibitor, and an agent that stimulates metabolism of body fat.

24. A method of treatment or prevention of type II diabetes in a human being or animal, comprising the step of administering to said human being or animal in need thereof a therapeutically effective amount of a compound according to claim 1 in combination or association with a therapeutically effective amount of an anti-diabetic agent.