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- Nachgewiesen in: USPTO Patent Applications
- Sprachen: English
- Document Number: 20070066600
- Publication Date: March 22, 2007
- Appl. No: 11/510324
- Application Filed: August 25, 2006
- Claim: 1. A compound of the formula II: [chemical expression included] or a pharmaceutically acceptable salt thereof, wherein: P is [chemical expression included] P and R3 are bound to the same ring and are disposed in meta- or para-positions relative to each other; R1 is (a) C1-6 alkyl, (b) C1-6 alkoxyalkyl, (c) straight or branched C1-6 hydroxyalkyl, (d) straight or branched C1-6 alkylhalides; or (e) a group Ar; Ar is (a) phenyl, (b) 1-naphthyl, (c) 2-naphthyl, (d) benzyl, (e) cinnamoyl, (f) a 5 to 7-membered, optionally aromatic, partially saturated or completely saturated, heterocyclic ring containing 1 to 4 heteroatoms, selected from oxygen, nitrogen and sulfur, or (g) a bicyclic ring system comprising at least one heterocyclic ring according to (f). wherein the group Ar is substituted in one or more positions with (a) H, X or Y, or (b) a 5 to 7-membered, optionally aromatic, partially saturated or completely saturated, heterocyclic ring each containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulfur; R2 is (a) H, (b) C1-6 alkyl, (c) C1-6 alkoxy, (d) straight or branched C1-6 hydroxyalkyl, or (e) straight or branched C1-6 alkylhalides; or R1 and R2 are linked to form a group (CH2)4O; One of R3 is a group [chemical expression included] X and Y are independently (a) H, (b) halogen, (c) C1-6 alkyl, (d) —CF3, (e) hydroxy, (f) C1-6 alkoxy, (g) C1-4 alkenyl; (h) phenyl; (i) phenoxy, (j) benzyloxy, (k) benzoyl, (l) —OCF3, (m) —CN, (n) straight or branched C1-6 hydroxyalkyl, (o) straight or branched C1-6 alkylhalides, (p) —NH2, (q) —NHR4, (r) —NR4R5, (s) —NO2, (t) —CONR4R5, (u) —NHSO2R4, (v) —NR4COR5, (x) —SO2NR4R5, (z) —C(═O)R4, (aa) —CO2R4, (ab) —S(O)nR4; wherein n is 0, 1, 2 or 3; (ac) —S—(C1-6)alkyl or (ad) —SCF3; R4 and R5 are independently (a) H, (b) C1-6 alkyl, (c) C3-7 cycloalkyl, or (d) Ar, as defined above for R1; alternatively, R4 and R5 are linked to form a group (CH2)2O, (CH2)4O or (CH2)3-5; and R6 is (a) H, or (b) straight of branched C1-6 alkyl.
- Claim: 2-6. (canceled)
- Claim: 7. The compound according to claim 1, wherein R1 is (a) C1-6 alkyl, or (e) a group Ar; Ar is (a) phenyl, (b) 1-naphthyl, (c) 2-naphthyl, or (f) a 5 to 7-membered, optionally aromatic, partially saturated or completely saturated, heterocyclic ring containing 1 to 4 heteroatoms, selected from oxygen, nitrogen and sulfur; wherein the group Ar is substituted in one or more positions with X or Y; wherein X or Y is (a) H, (b) halogen, (c) C1-6 alkyl, (d) —CF3, (f) C1-6 alkoxy, (g) C1-4 alkenyl; (l) —OCF3, or (n) straight or branched C1-6 hydroxyalkyl. R2 is (a) H, or (b) C1-3 alkyl, in particular methyl; or R1 and R2 are linked to form a group (CH2)4O; and R3 is [chemical expression included] wherein R6 is (a) H, or (b) C1-6 alkyl, in particular methyl.
- Claim: 8. The compound according to claim 1, wherein the compound is selected from the group consisting of: N-(4-Methylphenyl)-4-(1-piperazinyl)-1-naphthalenesulfonamide, hydrochloride; N-(2,4-Dimethoxyphenyl)-4-(1-piperazinyl)-1-naphthalenesulfonamide, hydrochloride; N-(3,4-di-Fluorophenyl)-4-(4-methyl-1,4-diazepan-1-yl)-1-naphthalenesulfonamide, hydrochloride; N-(3-Fluorophenyl)-4-(4-methyl-1,4-diazepan-1-yl)-1-naphthalenesulfonamide, hydrochloride; 4-(4-Ethyl-1-piperazinyl)-N-phenyl-1-naphthalenesulfonamide, hydrochloride; 4-Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl-N-(4-methylphenyl)-1-naphthalenesulfonamide, hydrochloride; N-(3,4-Dimethoxyphenyl)-4-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl-1-naphthalenesulfonamide, hydrochloride; 4-(4-Ethyl-1-piperazinyl)-N-(4-methylphenyl)-1-naphthalenesulfonamide, hydrochloride; N-(3,4-Dimethoxyphenyl)-4-(3-methyl-1-piperazinyl)-1-naphthalenesulfonamide, hydrochloride; N-(4-Methylphenyl)-4-(4-methyl-1-piperazinyl)-1-naphthalenesulfonamide, hydrochloride; N-[4-(2,5-Diazabicyclo[2.2.1]hept-2-yl)-1-naphthyl]-4-methylbenzenesulfonamide, hydrochloride; N-(4-Methylphenyl)-4-(3-methyl-1-piperazinyl)-1-naphthalenesulfonamide, hydrochloride; N-(2-Naphthyl)-4-(1-piperazinyl)-1-naphthalenesulfonamide, hydrochloride; N-Methyl-N-(4-methylphenyl)-4-(1-piperazinyl)-1-naphthalenesulfonamide, hydrochloride; 4-(1,4-Diazepan-1-yl)-N-(4-methylphenyl)-1-naphthalenesulfonamide, hydrochloride; 4-(1,4-Diazepan-1-yl)-N-(2-methoxy-4-methylphenyl)-1-naphthalenesulfonamide, hydrochloride; N-(2-Methoxy-4-methylphenyl)-4-(3,5-trimethyl-1-piperazinyl)-1-naphthalenesulfonamide, hydrochloride; 4-(4-Isopropyl-1-piperazinyl)-N-(4-methylphenyl)-1-naphthalenesulfonamide, hydrochloride; 4-Bromo-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 2,5-di-Chloro-N-[4-(1-piperazinyl)-1-naphthyl]benzenesulfonamide, hydrochloride; 2-Chloro-4-fluoro-N-[4-(1-piperazinyl)-1-naphthyl]benzenesulfonamide, hydrochloride; 2,3-di-Chloro-N-[4-(1-piperazinyl)-1-naphthyl]benzenesulfonamide, hydrochloride 2,4-di-Chloro-5-methyl-N-[4-(1-piperazinyl)-1-naphthyl]benzenesulfonamide, hydrochloride; 3-tri-Fluoromethyl-N-[4-(1-piperazinyl)-1-naphthyl]benzenesulfonamide, hydrochloride; 2-tri-Fluoromethyl-N-[4-(1-piperazinyl)-1-naphthyl]benzenesulfonamide, hydrochloride; 4-Bromo-N-methyl-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; Naphthalene-1-sulfonic acid (4-piperazin-1-yl-naphthalen-1-yl)-amide, hydrochloride; Naphthalene-1-sulfonic acid (4-piperazin-1-yl-naphthalen-1-yl)-amide, hydrochloride; 2,5-Dichloro-thiophene-3-sulfonic acid (4-piperazin-1-yl-naphthalen-1-yl)-amide, hydrochloride; 4-Methoxy-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 4-Chloro-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 2-Chloro-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; N-(4-piperazin-1-yl-naphthalen-1-yl)-4-trifluoromethyl-benzenesulfonamide, hydrochloride; 4-Fluoro-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 5-Fluoro-2-methyl-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 4-Phenoxy-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 2-Bromo-4-iodo-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; Thiophene-2-sulfonic acid (4-piperazin-1-yl-naphthalen-1-yl)-amide, hydrochloride; 5-Chloro-thiophene-2-sulfonic acid (4-piperazin-1-yl-naphthalen-1-yl)-amide, hydrochloride; 3-Methyl-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 4-Butyl-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide hydrochloride; 2,4,6-Trimethyl-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide hydrochloride; 2,4,5-Trichloro-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 4-Iodo-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 2-Methyl-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 3,4-Dichloro-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 5-Bromo-2-methoxy-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 2-Bromo-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 3-Chloro-2-methyl-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 2,6-Dichloro-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 3-Methoxy-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 3-Chloro-4-methyl-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 4-Bromo-2-fluoro-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 2,4-Dichloro-6-methyl-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 4-Bromo-2-methyl-N-(4-piperazin-1-yl-naphthalen-1-yl)-benzenesulfonamide, hydrochloride; 4,5-Dichloro-thiophene-2-sulfonic acid (4-piperazin-1-yl-naphthalen-1-yl)-amide, hydrochloride; N-Methyl-N-(4-bromo-2-methylphenyl)-4-(1-pyperazinyl)-1-napthalenesulphonamide, hydrochloride; N-Methyl-N-(5-fluoro-2-methylphenyl)-4-(1-pyperazinyl)-1-napthalenesulphonamide, hydrochloride; N-Methyl-N-(2-methylphenyl)-4-(1-pyperazinyl)-1-napthalenesulphonamide, hydrochloride; N-Methyl-N-(3-chloro-2-methylphenyl)-4-(1-pyperazinyl)-1-napthalenesulphonamide, hydrochloride; 2,5-di-Chlorothiophen-3-yl-N-Methyl-N-(2,5-dichlorothiophen-3-yl)-4-(1-pyperazinyl)-1-napthalenesulphonamide, hydrochloride; N-Methyl-N-(2-naphthyl)-4-(1-pyperazinyl)-1-napthalenesulphonamide, hydrochloride; N-Methyl-N-(1-naphthyl)-4-(1-pyperazinyl)-1-napthalenesulphonamide, hydrochloride; N-Methyl-N-(4-chlorophenyl)-4-(1-pyperazinyl)-1-napthalenesulphonamide, hydrochloride; N-Methyl-N-(4-methoxyphenyl)-4-(1-pyperazinyl)-1-napthalenesulphonamide, hydrochloride; 5-Fluoro-2-methyl-N-{4-[(2R,5S)-2,5-dimethyl-1-]piperazin-1-yl-1-naphthyl}benzenesulfonamide, hydrochloride; 5-Fluoro-2-methyl-N-[4-(1,2,3,6-tetrahydropyridin-4-yl)-1-naphthyl]benzenesulfonamide, hydrochloride; N-[4-(4-Methyl-1-piperazinyl)-2-naphthyl]benzenesulfonamide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid phenylamide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (2-methoxy-phenyl)-amide, hydrochloride; 4-(cis-3,5-Dimethyl-piperazin-1-yl)-naphthalene-1-sulfonic acid (2-methoxy-phenyl)-amide, hydrochloride; 4-(cis-3,5-Dimethyl-piperazin-1-yl)-naphthalene-1-sulfonic acid (3-chloro-phenyl)-amide, hydrochloride; 4-[1,4]Diazepan-1-yl-naphthalene-1-sulfonic acid (3-chloro-phenyl)-amide, hydrochloride; 4-[1,4]Diazepan-1-yl-naphthalene-1-sulfonic acid phenylamide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (3-chloro-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (2-methylsulfanyl-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid methyl-naphthalen-1-yl-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (2,3-dihydro-benzo[1,4]dioxin-6-yl)-methyl-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (2,3-dihydro-benzo[1,4]dioxin-6-yl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid methyl-(2-methylsulfanyl-phenyl)-amide, hydrochloride; 4-Piperazin-1-yl-naphthalene-1-sulfonic acid methyl-(3-trifluoromethyl-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (3-chloro-4-methyl-phenyl)-methyl-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (3-ethyl-phenyl)-methyl-amide, hydrochloride; 4-(3,5-Dimethyl-piperazin-1-yl)-naphthalene-1-sulfonic acid (2-isopropyl-phenyl)-amide, hydrochloride; 4-[1,4]Diazepan-1-yl-naphthalene-1-sulfonic acid (2-isopropyl-phenyl)-amide, hydrochloride; 4-[1,4]Diazepan-1-yl-naphthalene-1-sulfonic acid (3-ethyl-phenyl)-amide, hydrochloride, N-(2-Fluorophenyl)-4-piperazin-1-ylnaphthalene-1-sulfonamide, hydrochloride; 4-[1,4]Diazepan-1-yl-naphthalene-1-sulfonic acid (3-trifluoromethyl-phenyl)-amide, hydrochloride; N-(2,4-di-Fluorophenyl)-4-piperazin-1-ylnaphthalene-1-sulfonamide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (2-trifluoromethoxy-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (3-3-phenoxyphenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (3-trifluoromethoxy-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (2-chloro-5-methyl-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (3-trifluoromethoxy-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (2-chloro-5-methyl-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (4-isopropyl-phenyl)-amide, hydrochloride; N-(3,5-di-Fluorophenyl)-4-piperazin-1-ylnaphthalene-1-sulfonamide, hydrochloride; 1-[4-(3,4-Dihydroquinolin-1(2H)-ylsulfonyl)-1-naphthyl]piperazine, hydrochloride; 4-[1,4]Diazepan-1-yl-naphthalene-1-sulfonic acid (3-nitro-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (3-nitro-phenyl)-amide, hydrochloride; 4-[1,4]Diazepan-1-yl-naphthalene-1-sulfonic acid (3-nitro-phenyl)-methyl-amide, hydrochloride; N-(4-Methylphenyl)-4-piperazin-1-ylnaphthalene-1-sulfonamide, hydrochloride; N-(3-Chloro-4-methylphenyl)-4-piperazin-1-ylnaphthalene-1-sulfonamide, hydrochloride; 4-[1,4]Diazepan-1-yl-naphthalene-1-sulfonic acid (2,3-dimethyl-phenyl)-methyl-amide, hydrochloride; 4-[1,4]Diazepan-1-yl-naphthalene-1-sulfonic acid (4-isopropyl-phenyl)-amide, hydrochloride; 4-[1,4]Diazepan-1-yl-naphthalene-1-sulfonic acid (4-isopropyl-phenyl)-methyl-amide, hydrochloride; 4-[1,4]Diazepan-1-yl-naphthalene-1-sulfonic acid (2,4-dimethyl-phenyl)-amide, hydrochloride; 4-[1,4]Diazepan-1-yl-naphthalene-1-sulfonic acid (2-chloro-5-methyl-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (2,5-dimethoxy-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (3-acetyl-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (2,4-dimethyl-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (3-trifluoromethyl-phenyl)-amide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid biphenyl-2-ylamide, hydrochloride; 4-piperazin-1-yl-naphthalene-1-sulfonic acid (3-benzyloxy-phenyl)-amide, hydrochloride; N-(4-fluorophenyl)-4-piperazin-1-ylnaphthalene-1-sulfonamide, hydrochloride; N-(3-Ethylphenyl)-4-piperazin.1.ylnaphthalene-1-sulphonamine, hydrochloride; 4-piperazinyl-N-[3-(trifluoromethyl)phenyl]naphthalene-1-sulfonamide, hydrochloride; 4-piperazinyl-N-[3-benzoylphenyl]naphthalene-1-sulfonamide, hydrochloride; 4-piperazinyl-N-[3-(4-bromo-1-methyl-1H-pyrazol-3-yl)phenyl]naphthalene-1-sulfonamide, hydrochloride; and 4-piperazinyl-N-[3-biphenylphenyl]naphthalene-1-sulfonamide, hydrochloride.
- Claim: 9-12. (canceled)
- Claim: 13. A process for the preparation of a compound according to claim 1, wherein P is [chemical expression included] said method comprising the steps of: (a) nucleophilic aromatic substitution of the aromatic halogen atom in 1-chloro-3-nitronaphthalene or 1-chloro-4-nitronaphthalene with aliphatic or aromatic diamines; (b) reduction of the nitro group in 1-diamine-3-nitronaphthalene or 1-diamine-4-nitronaphthalene obtained in step (a) to form 1-diamine-3-NH2-naphthalene or 1-diamine-4-NH2-naphthalene, respectively; and (c) synthesis of a sulfonamide by reacting 1-diamine-3-NH2-naphthalene or 1-diamine-4-NH2-naphthalene obtained in step (b) with a suitable sulfonyl chloride.
- Claim: 14. The process of claim 13, wherein step (a) is by means of Palladium catalyzed nucleophilic substitution.
- Claim: 15. A process for the preparation of a compound according to claim 1, wherein P is [chemical expression included] said method comprising the steps of: (a) nucleophilic aromatic substitution of the trifluoromethanesulfonate group in 2-trifluoromethansulfonate-5-nitroquinoline with aliphatic or aromatic diamines; (b) reduction of the nitro group in 2-diamine-5-nitroquinoline obtained in step (a) to form 2-diamine-5-NH2-quinoline; and (c) synthesis of a sulfonamide by reacting 2-diamine-5-NH2-quinoline obtained in step (b) with a suitable sulfonyl chloride.
- Claim: 16. A process for the preparation of a compound according to claim 1, wherein P is [chemical expression included] said method comprising the steps of: (a) reacting a fluoronaphthalene and chlorosulfonic acid under acidic conditions, to introduce a sulfonyl chloride group in the para position to the carbon having the fluoro atom; (b) reacting the product of step (a) with an aliphatic or aromatic primary amine to give a sulphonamide; and (c) reaction of the product of step (b) with a diamine.
- Claim: 17. A pharmaceutical formulation containing a compound according to claim 1 as active ingredient, in combination with a pharmaceutically acceptable diluent or carrier.
- Claim: 18. A method for the treatment or prophylaxis of obesity, type II diabetes, and/or disorders of the central nervous system, which comprises administering to a mammalin need of such treatment an effective amount of a compound according to claim 1.
- Claim: 19. A method for reducing body-weight or reducing food intake, comprising administering to a subject in need thereof an effective amount of a compound according to claim 1.
- Claim: 20. A method for modulating 5-HT6 receptor activity, comprising administering to a subject in need thereof an effective amount of a compound according to claim 1.
- Current U.S. Class: 514218/000
- Current International Class: 61; 61; 61; 61; 61; 61
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