Substituted sulfonamide compounds useful for the prophylaxis and treatment of conditions relating to obesity, type II diabetes and/or disorders of the central nervous system

1. A compound of the formula (I)

or a pharmaceutically acceptable salt thereof, wherein

X is

R 1 is a group Ar;

R 3 is:

(a) H

(b) C 1-6 alkyl,

(c) C 1-6 alkoxy,

(d) straight or branched C 1-6 hydroxyalkyl,

(e) straight or branched C 1-6 alkylhalides; or

(f) a group Ar;

each Ar is

(a) phenyl,

(b) 1-naphthyl,

(c) 2-naphthyl,

(d) benzyl,

(e) cinnamoyl,

(f) a 5 to 7-membered, partially or completely saturated, heterocyclic ring containing 1 to 4 heteroatoms, selected from oxygen, nitrogen and sulfur, or

(g) a bicyclic ring system consisting of two heterocyclic rings as defined under (f), or a bicyclic ring system consisting of one benzene ring and one heterocyclic ring as defined under (f);

alternatively, R 1 and R 3 are linked to form a group (CH 2 ) 3-5 in formula (Ib);

optionally, the group Ar is substituted with one or more substituents selected from the group consisting of

(a) halogen,

(b) C 1-6 alkyl,

(c) CF 3 ,

(d) hydroxy,

(e) C 1-6 alkoxy,

(f) C 1-4 alkenyl;

(g) phenyl;

(h) phenoxy,

(i) benzyloxy,

(j) benzoyl,

(k) OCF 3 ,

(l) CN,

(m) straight or branched C 1-6 hydroxyalkyl,

(n) straight or branched C 1-6 alkylhalides,

(o) NH 2 ,

(p) NHR 6 ,

(q) NR 6 R 7 ,

(r) NO 2 ,

(s) —CONR 6 R 7 ,

(t) NHSO 2 R 6 ,

(u) NR 6 COR 7 ,

(v) SO 2 NR 6 R 7 ,

(w) —C(═O)R 6 ,

(x) —CO 2 R 6 , or

(y) S(O) n R 6 ; wherein n is 0, 1, 2 or 3; and

(z) a 5 to 7-membered, partially or completely saturated, heterocyclic ring each containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulfur;

Y is

(a) H,

(b) halogen,

(c) C 1-6 alkyl,

(d) CF 3 ,

(e) hydroxy,

(f) C 1-6 alkoxy,

(g) C 1-4 alkenyl;

(h) phenyl;

(i) phenoxy,

(j) benzyloxy,

(k) benzoyl,

(l) OCF 3 ,

(m) CN,

(n) straight or branched C 1-6 hydroxyalkyl,

(o) straight or branched C 1-6 alkylhalides,

(p) NH 2 ,

(q) NHR 6 ,

(r) NR 6 R 7 ,

(s) NO 2 ,

(t) —CONR 6 R 7 ,

(u) NHSO 2 R 6 ,

(v) NR 6 COR 7 ,

(x) SO 2 NR 6 R 7 ,

(z) —C(═O)R 6 ,

(aa) —CO 2 R 6 , or

(ab) S(O) n R 6 ; wherein n is 0, 1, 2 or 3;

R 2 and R 4 are independently:

(a) —SO 2 R 1 ,

(b) H,

(c) C 1-6 alkyl,

(d) C 1 -C 3 alkenyl,

(e) C 1 -C 3 alkylaryl,

(f) Ar as defined above for R 1 ,

(g) —C(═O)R 6 ,

(h) —C(O)NR 6 R 7 ,

(i) —C(S)NR 6 R 7 ,

(j) —CO 2 R 6 ;

(k) —C(S)R 6 ;

(l) straight or branched C 1-6 hydroxyalkyl, or

(m) straight or branched C 1-6 alkylhalides;

alternatively, R 2 and R 4 are linked to form a group (CH 2 ) 3-5 in formula (Ia);

R 5 is selected from the group consisting of the following chemical groups:

each R 6 and R 7 is independently

(a) H,

(b) C 1-6 alkyl,

(c) C 3-7 cycloalkyl, or

(d) Ar 1 ;

wherein each Ar 1 is

(a) phenyl,

(b) 1-naphthyl,

(c) 2-naphthyl,

(d) benzyl,

(e) cinnamoyl,

(f) a 5 to 7-membered, partially or completely saturated, heterocyclic ring containing 1 to 4 heteroatoms, selected from oxygen, nitrogen and sulfur, or

(g) a bicyclic ring system consisting of two heterocyclic rings as defined under (f), or a bicyclic ring system consisting of one benzene ring and one heterocyclic ring as defined under (f);

optionally, the group Ar 1 is substituted with one or more substituents selected from the group consisting of

(a) halogen,

(b) C 1-6 alkyl,

(c) CF 3 ,

(d) hydroxy,

(e) C 1-6 alkoxy,

(f) C 1-4 alkenyl;

(g) phenyl;

(h) phenoxy,

(i) benzyloxy,

(j) benzoyl,

(k) OCF 3 ,

(l) CN,

(m) straight or branched C 1-6 hydroxyalkyl,

(n) straight or branched C 1-6 alkylhalides,

(o) NH 2 ,

(p) NHR 9 ,

(q) NR 9 R 10 ,

(r) NO 2 ,

(s) —CONR 9 R 10 ,

(t) NHSO 2 R 9 ,

(u) NR 9 COR 10 ,

(v) SO 2 NR 9 R 10 ,

(w) —C(═O)R 9 ,

(x) —CO 2 R 9 , or

(y) S(O) n R 9 ; wherein n is 0, 1, 2 or 3; and

(z) a 5 to 7-membered, partially or completely saturated, heterocyclic ring each containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulfur;

alternatively, R 6 and R 7 are linked to form a group (CH 2 ) 3-5 ;

R 8 is

(a) H, or

(b) C 1-6 alkyl; and

each R 9 and R 10 is independently

(a) H,

(b) C 1-6 alkyl; or

(c) C 3-7 cycloalkyl; or

alternatively, R 9 and R 10 are linked to form a group (CH 2 ) 3-5 .

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

Ar is

(a) phenyl,

(b) 1-naphthyl,

(c) 2-naphthyl, or

(f) a 5 to 7-membered, partially or completely saturated, heterocyclic ring containing 1 to 4 heteroatoms, selected from oxygen, nitrogen and sulfur;

the group Ar is optionally substituted one or more substituents selected from the group consisting of

(a) halogen,

(b) C 1-6 alkyl,

(c) CF 3 ,

(d) C 1-6 alkoxy,

(e) C 1-4 alkenyl;

(f) phenyl;

(g) OCF 3 , and

(h) straight or branched C 1-6 hydroxyalkyl.

3. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein

the group

is attached to the phenyl ring in 2-position and 3-position.

4. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is —SO 2 R 1 .

5. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 and R 4 are independently H, methyl or ethyl.

6. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 6 and R 7 is independently

(a) H,

(b) C 1-6 alkyl,

(c) C 3-7 cycloalkyl, or

(d) Ar 1 .

7. A compound according to claim 1 , which is the compound

3-amino-4-(hexahydro-pyrrolo[1,2-α]pyrazin-2-yl)-N-(2-methoxyphenyl)-benzenesulfonamide;

3-amino-4-(hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)N-phenyl-benzenesulfonamide; or

3-amino-4-(5-methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-N-phenyl-benzenesulfonamide;

or a pharmaceutically acceptable salt of such a compound.

8. A pharmaceutical formulation comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, as an active ingredient, in combination with a pharmaceutically acceptable diluent or carrier.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ar is a 5 to 7-membered aromatic heterocyclic ring containing 1 to 4 heteroatoms, selected from oxygen, nitrogen and sulfur.

10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein Ar is isoxazolyl, benzoxadiazol, quinolinyl, or thienyl.

11. A method for the treatment of obesity, the method comprising administering to a mammal in need of such treatment an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

12. A method for the reduction of food intake, the method comprising administering to a mammal in need of such treatment an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

13. The method of claim 12 , wherein the mammal in need of such treatment is an obese mammal.

14. A method for the treatment of a disorder of the central nervous system selected from the group consisting of anxiety, depression, sleep disorders, and schizophrenia, the method comprising administering to a mammal in need of such treatment an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

15. The method of claim 14 , wherein the disorder is depression.

16. The method of claim 14 , wherein the disorder is anxiety.

17. The method of claim 14 , wherein the disorder is schizophrenia.

18. The method of claim 14 , wherein the disorder is sleep disorders.

19. A method for the treatment of type II diabetes, the method comprising administering to a mammal in need of such treatment an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

20. A method for the treatment of a disorder of the central nervous system wherein the disorder is a memory disorder, the method comprising administering to a mammal in need of such treatment an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.