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- Nachgewiesen in: USPTO Patent Grants
- Sprachen: English
- Patent Number: 7,173,035
- Publication Date: February 06, 2007
- Appl. No: 10/143335
- Application Filed: May 10, 2002
- Assignees: Biovitrum AB (SE)
- Claim: 1. A compound of the formula (I) [chemical expression included] or a pharmaceutically acceptable salt thereof, wherein X is [chemical expression included] R 1 and R 3 are independently (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; 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) 2 O, (CH 2) 4 O, or (CH 2) 3-5 in formula (Ib); optionally, the group Ar is substituted with (a) Y, or (b) 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) NHSO 2 R 6 , (u) NR 6 COR 7 , or (v) —CO 2 R 6 ; 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) 2 O, (CH 2) 4 O, or (CH 2) 3-5 in formula (I); R 5 is selected from the group consisting of the following chemical groups: [chemical expression included] R 6 and R 7 are independently (a) H, (b) C 1-6 alkyl, (c) C 3-7 cycloalkyl, or (d) Ar, as defined above for R 1 ; alternatively, R 6 and R 7 are linked to form a group (CH 2) 2 O, (CH 2) 4 O or (CH 2) 3-5 ; R 8 is (a) H, or (b) C 1-6 alkyl.
- Claim: 2. A compound according to claim 1 wherein R 1 is a group Ar; 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 substituted with Y, wherein Y is (a) H, (b) halogen, (c) C 1-6 alkyl, (d) CF 3 , (f) C 1-6 alkoxy, (g) C 1-4 alkenyl; (h) phenyl; (l) OCF 3 , or (n) straight or branched C 1-6 hydroxyalkyl.
- Claim: 3. A compound according to claim 1 , wherein the group [chemical expression included] is attached to the phenyl ring in 2-position and 3-position.
- Claim: 4. A compound according to claim 1 , wherein R 2 is —SO 2 R 1 .
- Claim: 5. A compound according to claim 1 , wherein R 3 and R 4 are independently H, methyl or ethyl.
- Claim: 6. A compound according to claim 1 , wherein R 5 is selected from the group consisting of the following chemical groups: [chemical expression included] wherein R 8 is H or methyl.
- Claim: 7. A compound according to claim 1 , wherein R 6 and R 7 are independently (a) H, (b) C 1-6 alkyl, (c) C 3-7 cycloalkyl, or (d) Ar.
- Claim: 8. A compound according to claim 1 , wherein the compound is selected from the group consisting of: N-[2-{ethyl[(3-fluorophenyl)sulfonyl]amino}-4-(4-methyl-1-piperazinyl)phenyl]-3-fluorobenzenesulfonamide, N-[2-[ethyl(phenylsulfonyl)amino]-4-(4-methyl-1-piperazinyl)phenyl]benzenesulfonamide, 3-fluoro-N-[2-{[(3-fluorophenyl)sulfonyl]amino}-4-(4-methyl-1-piperazinyl) phenyl]benzenesulfonamide, N-{5-(4-methyl-1-piperazinyl)-2-[(8-quinolinylsulfonyl)amino]phenyl}-7-quinolinesulfonamide, N-[2-chloro-4-({4-(4-methyl-1-piperazinyl)-2-[(phenylsulfonyl)amino]anilino}sulfonyl)phenyl]acetamide, 3,4-dimethoxy-N-{4-(4-methyl-1-piperazinyl)-2-[(phenylsulfonyl)amino]phenyl}benzenesulfonamide, 3-methoxy-4-methyl-N-{4-(4-methyl-1-piperazinyl)-2-[(phenylsulfonyl)amino]phenyl}benzenesulfonamide, 4-methyl-N-{4-(4-methyl-1-piperazinyl)-2-[(methylsulfonyl)amino]phenyl}benzenesulfonamide, 3,4-dimethoxy-N-{4-(4-methyl-1-piperazinyl)-2-[(methylsulfonyl)amino]phenyl}benzenesulfonamide, 3-cyano-N-{4-(4-methyl-1-piperazinyl)-2-[(methylsulfonyl)amino]phenyl}benzenesulfonamide, N-{4-(1-piperazinyl)-2-[(phenylsulfonyl)amino]phenyl}-1-naphthalenesulfonamide, 5-(dimethylamino)-N-{4-(1-piperazinyl)-2-[(phenylsulfonyl)amino]phenyl}-1-naphthalenesulfonamide, N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]-8-quinolinesulfonamide, 2,4,6-trimethyl-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]benzenesulfonamide, 4-methyl-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]benzenesulfonamide, 2,5-dimethoxy-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]benzenesulfonamide, 2-methyl-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]benzenesulfonamide, 2,4-difluoro-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]benzenesulfonamide, 4-butoxy-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]benzenesulfonamide, 3,5-dimethyl-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]-4-isoxazolesulfonamide, 5-fluoro-2-methyl-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]benzenesulfonamide, 4-(methylsulfonyl)-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]benzenesulfonamide, 2-(methylsulfonyl)-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]benzenesulfonamide, 2-methoxy-4-methyl-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]benzenesulfonamide, 4-methoxy-2-methyl-N-[2-[(phenylsulfonyl)amino]-4-(1-piperazinyl)phenyl]benzenesulfonamide, N-[2-amino-4-(1-piperazinyl)phenyl]-3-fluorobenzenesulfonamide, N-[2-(ethylamino)-4-(1-piperazinyl)phenyl]-3-fluorobenzenesulfonamide, 3-amino-N-(3-chlorophenyl)-4-(4-methyl-1-piperazinyl)benzenesulfonamide hydrochloride, 3-amino-N-(2-methoxyphenyl)-4-(4-methyl-1-piperazinyl)benzenesulfonamide hydrochloride, 3-amino-N-(2-methoxyphenyl)-4-(1-piperazinyl)benzenesulfonamide hydrochloride, 3-amino-N-phenyl-4-piperazin-1-yl-benzenesulfonamide hydrochloride, 3-amino-4-(4-ethyl-piperazin-1-yl)-N-phenyl-benzenesulfonamide hydrochloride, 3-amino-4-(trans-2,5-dimethylpiperazin-1-yl)-N-(2-methoxy-phenyl)benzenesulfonamide hydrochloride, and 3-amino-2-chloro-N-naphthalen-1-yl-4-piperazin-1-yl-benzenesulfonamide, hydrochloride.
- Claim: 9. A process for the preparation of a compound of claim 1 comprising: (a) introduction of a cyclic diamine into a halogen and nitro substituted benzene under mild and basic conditions; (b) reduction of the nitro to a corresponding amine; (c) symmetric or asymmetric sulfonylation of the amine by a sulfonylchloride; (d) introduction of groups R 3 and R 4 by alkylation reactions in basic conditions.
- Claim: 10. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable diluent or carrier.
- Claim: 11. A method for the treatment of obesity, comprising administering to a mammal in need of such treatment an effective amount of a compound of claim 1 .
- Claim: 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 .
- Claim: 13. The method of claim 12 , wherein the mammal in need of such treatment is an obese mammal.
- Claim: 14. A method for the treatment of a disorder of the central nervous system selected from anxiety, depression, panic attacks, memory disorders, sleep disorders, binge disorders, migraine, anorexia, bulimia, obsessive compulsive disorders, psychoses, Alzheimer's disease, Parkinson's disease, Huntington's chorea, schizophrenia, and/or Attention Deficit Hyperactive Disorder, the method comprising administering to a mammal in need of such treatment an effective amount of a compound of claim 1 .
- Claim: 15. The method of claim 14 , wherein the disorder is depression.
- Claim: 16. The method of claim 14 , wherein the disorder is anxiety.
- Claim: 17. The method of claim 14 , wherein the disorder is schizophrenia.
- Claim: 18. The method of claim 14 , wherein the disorder is sleep disorders.
- Claim: 19. A compound of the formula (II) [chemical expression included] or a pharmaceutically acceptable salt thereof, wherein R 9 , R 12 and R 14 are H; or two of R 9 , R 12 and R 14 are H; and the remaining of R 9 , R 12 and R 14 is (a) —NH 2 , (b) —NHR 6 , (c) —NR 6 R 7 , (d) —NH(CO)R 6 , (e) —NH(CS)R 6 , or (f) —NO 2 ; R 10 is a group R 3 ; R 11 is a group R 1 ; in which each of R 1 and R 3 , independently, 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; 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 hetero cyclic ring as defined under (f); alternatively, R 1 and R 3 are linked to form a group (CH 2) 2 O, (CH 2) 4 O, or (CH 2) 3-5 ; optionally, the group Ar is substituted with (a) Y, or (b) 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 H; R 13 is a group R 5 ; and is selected from the group consisting of the following chemical groups: [chemical expression included] R 6 and R 7 are independently (a) H, (b) C 1-6 alkyl, (c) C 3-7 cycloalkyl, or (d) Ar, as defined above for R 1 ; alternatively, R 6 and R 7 are linked to form a group (CH 2) 2 O, (CH 2) 4 O or (CH 2) 3-5 ; R 8 is (a) H, or (b) C 1-6 alkyl.
- Claim: 20. A compound according to claim 19 wherein R 13 is a group R 5 selected from [chemical expression included] and R 8 is (a) H, or (b) C 1-6 alkyl; with the proviso that only one of R 9 , R 12 and R 14 is —NH 2 , —NHR 6 , —NR 6 R 7 , —NH(CO)R 6 , —NH(CS)R 6 , —NO 2 ; the other ones are H.
- Claim: 21. A compound according to claim 19 , which is the compound N-[4-nitro-5-(piperazinyl)phenyl]benzenesulfonamide, or N-[4-amino-5-(piperazinyl)phenyl]benzenesulfonamide.
- Claim: 22. A process for the preparation of a compound of claim 19 comprising: (a) introduction of a cyclic diamine into a halogen and nitro substituted benzene under mild and basic conditions; (b) reduction of the nitro to a corresponding amine; (c) selective introduction of a sulfonylamide group by a sulphonylchloride reacting with the amine; (d) introduction of a sulfonylanimo group by an aromatic nucleophilic substitution reaction.
- Claim: 23. A pharmaceutical composition comprising a compound of claim 19 and a pharmaceutically acceptable diluent or carrier.
- Claim: 24. A method for the treatment of a disorder of the central nervous system selected from anxiety, depression, panic attacks, memory disorders, sleep disorders, binge disorders, migraine, anorexia, bulimia, obsessive compulsive disorders, psychoses, Alzheimer's disease, Parkinson's disease, Huntington's chorea, schizophrenia, and/or Attention Deficit Hyperactive Disorder, the method comprising administering to a mammal in need of such treatment an effective amount of a compound of claim 19 .
- Claim: 25. The method of claim 24 , wherein the disorder is depression.
- Claim: 26. The method of claim 24 , wherein the disorder is anxiety.
- Claim: 27. The method of claim 24 , wherein the disorder is schizophrenia.
- Claim: 28. The method of claim 24 , wherein the disorder is sleep disorders.
- Claim: 29. The compound of claim 20 , wherein R 8 is H or methyl.
- Claim: 30. A compound that is N-[2-({[(E)-2-phenylethenyl]sulfonyl}amino)-5 -(1-piperazinyl)phenyl]benzenesulfonamide.
- Claim: 31. A compound that is 3-amino-N-(2-methoxyphenyl)-4-(3-methyl-1-piperazinyl)benzenesulfonamide hydrochloride.
- Current U.S. Class: 51425/306
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- Primary Examiner: Coleman, Brenda
- Attorney, Agent or Firm: Fish & Richardson P.C.
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