Derivatives of sulphonamides, their preparation and use as medicaments
AssigneeLaboratories Del Dr. Esteve, S.A.
InventorsRamon Merce-Vidal, Blas Andaluz-Mataro, Jordi Frigola-Constansa
Life of this patent
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Abstract
The present invention relates to new derivatives of sulphonamides, with the general formula (I), as well as to their physiologically acceptable salts, the processes for their preparation, their application as medicaments in human and/or veterinary therapy and the pharmaceutical compositions that contain them 1
Claims10
A compound derived of sulphonamide with the general formula (I)
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- wherein
- a represents a substituent selected from among:
- A heteroaromatic ring of 5 or 6 members containing 1 or 2 heteroatoms selected from among oxygen. nitrogen and sulphur, optionally substituted by 1 or 2 halogen atoms, by a C1-C4 alkyl radical or by a phenyl or heteroaryl radical with 5 or 6 members containing 1 or 2 atoms of oxygen, nitrogen or sulphur;
- A bicyclic heteroaromatic ring containing 1 to 3 heteroatoms selected from among oxygen, nitrogen and sulphur, optionally substituted by 1 or 2 halogen atoms or by a C1-C4 alkyl radical,
- A group selected from among
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- R1 represents hydrogen, a C1-C4 alkyl radical or a benzyl radical;
- n represents 0, 1, 2, 3 or 4;
- R2 represents —NR4R5 or a group with formula
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- Wherein the dotted line represents an optional chemical bond;
- R3, R4 y R5 independently represent hydrogen or a C1-C4 alkyl;
- X, Y and Z independently represent hydrogen, fluorine, chlorine, bromine, a C1-C4 alkyl, a C1-C4,alkoxy, a C1-C4 alkylthio, trifluoromethyl, cyano, nitro and —NR4R5;
- W represents a bond between the two rings, CH2, O, S and NR4,
- m represents 0, 1, 2, 3 or 4,
- with the condition that when m=0 A is a substituted phenyl, or one of its physiologically acceptable salts.
2 A compound, according to claim 1, selected from among the following group:
- [1] N-[3-(2-diethylaminoethyl)-1H-indol-5-yl]-5-chloro-3-methylbenzo[b]thiophene-2-sulphonamide
- [2] N-[3-(2-diethylaminoethyl)-1H-indol-5-yl]naphthalene-1-sulphonamide.
- [3] Hydrochloride N-[3-(2-diethylaminoethyl)-1H-indol-5-yl]naphthalene-1-sulphonamide.
- [4] N-[3-(2-diethylaminoethyl)-1H-indol-5-yl]-3,5-dichlorobenzenesulphonamide.
- [5] N-[3-(2-diethylaminoethyl)-1H-indol-5-yl]-4-phenylbenzenesulphonamide.
- [6] N-[3-(2-diethylaminoethyl)-1H-indol-5-yl]-5-chlorothiophene-2-sulphonamide.
- [7] N-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-5-chloro-3-methylbenzo[b]thiophene-2-sulphonamide.
- [8] N-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]naphthalene-1-sulphonamide
- [9] N-[3-(2-dimethylamino-ethyl)-1H-indol-5-yl]-6-chloroimidazo[2,1-b]thiazol-5-sulphonamide.
- [10] N-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]-5-chloro-3-methylbenzo[b]thiophene-2-sulphonamide.
- [11] N-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]-5-chloro-3-methylbenzo[b]thiophene-2-sulphonamide hydrochloride
- [12] N-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]naphthalene-1-sulphonamide.
- [13] N-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]naphthalene-1-sulphonamide hydrochloride
- [14] N-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]-5-chlorothiophene-2-sulphonamide.
- [15] N-[3-(1-methylpiperdin-4-yl)-1H-indol-5-yl]-4-phenylbenzenesulphonamide.
- [16] N-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]quinoline-8-sulphonamide.
- [17] N-[3-(2-diethylaminoethyl)-1H-indol-5-yl]naphthalene-2-sulphonamide.
- [18] N-[3-(1-methyl-1 ,2,3,6-tetrahydropyridin-4-yl)-1H-indol-5-yl]naphthalene-1-sulphonamide.
- [19] N-[3-(4-methylpiperazin-1-yl )methyl-1H-indol-5-yl]-5-chloro-3-methylbenzo[b]thiophene-2-sulphonamide.
- [20] N-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-5-(2-pyridil)thiophene-2-sulphonamide.
- [21] N-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-2,1,3-benzothiadiazol-4-sulphonamide.
- [22] N-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]quinoline-8-sulphonamide.
- [23] N-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-5-chloronaphthalene-2-sulphonamide.
- [24] N-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-4-phenoxybenzenesulphonamide.
- [25] N-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-4-phenylbenzenesulphonamide.
- [26] N-[3-(2-diethylaminoethyl)-1H-indol-5-yl]-N-ethyl-naphthalene-2-sulphonamide.
- [27] N-{3-[2-(morpholin-4-yl}ethyl]-1H-indol-5-yl)-5-chloro-3-methylbenzo[b]thiophene-2-sulphonamide.
- [28] N-{3-[2-(morpholin-4-yl}ethyl]-1H-indol-5-yl)naphthalene-1-sulphonamide.
- [29] N-[3-(2-diethylaminoethyl)-1H-indol-5-yl]naphthalene-2-sulphonamide.
- [30] N-[3-dimethylaminomethyl-1H-indol-5-yl]-5-chloro-3-methylbenzo[b]thiophene-2-sulphonamide,
- [31] N-[3-(2-dipropylaminoethyl)-1H-indol-5-yl]naphthalene-1-sulphonamide.
- [32] N-[3-(2-dipropylaminoethyl)-1H-indol-5-yl]-5-chloro-3-methylbenzo[b]thiophene-2-sulphonamide.
- [33] N-[3-(2-dibutylaminoethyl)-1H-indol-5-yl]-5-chloro-3-methylbenzo[b]thiophene-2-sulphonamide.
- [34] N-[3-(2-dibutylaminoethyl)-1H-indol-5-yl]naphthalene-1-sulphonamide.
- [35] N-[3-(2-diethylaminoethyl)-1H-indol-5-yl]-5-chloronaphthalene-1-sulphonamide.
- [36] N-[3-(2-diethylaminoethyl)-1H-indol-5-yl]-trans-β-styrenesulphonamide.
- [37] N-[3-(4-methylpiperazin-1-yl)methyl-1H-indol-5-yl]-trans-β-styrenesulphonamide.
- [38] N-[3-(octahydroindolizin-7-yl)-1H-indol-5-yl]-5-chloro-3-methylbenzo[b]thiophene-2-sulphonamide.
- [39] N-[3-(2-diethylaminoethyl)-1H-indol-5-yl]-6-chloroimidazo[2, 1-b]thiazol-5-sulphonamide
- [40] N-{3-[2-(morpholin-4-yl)ethyl]-1H-indol-5-yl}naphthalene-2-sulphonamide
- [41] N-[3-(4-methylpiperazin-1-yl)methyl-1H-indol-5-yl]-α-toluenesulphonamide.
- [42] N-[3-(3-diethylaminopropyl)-1H-indol-5-yl]naphthalene-2-sulphonamide
- [43] N-[3-(3-diethylaminopropyl)-1H-indol-5-yl]-5-chloro-3-methylbenzo[b]thiophene-2-sulphonamide
- [44] N-{3-[2-(pyrrolidin-1-yl)ethyl]1H-indol-5-yl}-5-chloro-3-methylbenzo[b]thiophene-2-sulphonamide.
- [45] N-{3-[2-(pyrrolidin-1-yl)ethyl]-1H-indol-5-yl}naphthalene-1-sulphonamide.
- [46] N-{3-[2-(pyrrolidin-1-yl)ethyl]-1H-indol-5-yl}naphthalene-2-sulphonamide.
- [47] N-[3-(2-dipropylaminoethyl)-1H-indol-5-yl]naphthalene-2-sulphonamide
- [48] N-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-5-chloronaphthalene-1-sulphonamide.
- [49] N-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]naphthalene-2-sulphonamide.
- [50] N-{3-[2-(morpholin-4-yl)ethyl]-1H-indol-5-yl}quinoline-8-sulphonamide
- [51] N-{3-[2-(morpholin-4-yl)ethyl]-1H-indol-5-yl}-4-phenylbenzenesulphonamide
- [52] N-[3-(4-methylpiperazin-1-yl)ethyl-1H-indol-5-yl]naphthalene-2-sulphonamide.
- [53] N-[3-(4-methylpiperazin-1-yl)ethyl-1H-indol-5-yl]-5-chloronaphthalene-1-sulphonamide
4 Process for preparing a derivative of sulphonamide with the general formula (I), according to claim 1, wherein R1 R2, R4, n and A are as indicated above in claim 1, and R3 represents a C1-C4 alkyl. characterised by making react a compound with the general formula (I), wherein R1, R2, R4, n and A are as indicated above in claim 1, and R3 represents an atom of hydrogen, with an alkyl halogenide or dialkyl sulphate.
5 Process for preparing a derivative of sulphonamide with the general formula (I), according to claim 1, wherein R1, R3, and A are as indicated above in claim 1, n=0 and R2 represents a 1.2,3,6-tetrahydropyridin-4-yl radical substituted in position 1 with an R1 radical, characterised by making react a compound with the general formula (I), wherein R1, R3, and A are as indicated above in claim 1, n=0 and R2 represents an atom of hydrogen. with a 4-piperidone substituted in position 1 with an R1 radical
6 Process for preparing a derivative of sulphonamide with the general formula (I), according to claim 1, wherein R1, R3, and A are as indicated above in claim 1, n=0 and R2 represents a 4-piperidinyl radical substituted in position 1 with an R1 radical, by reduction of a compound with the general formula (I) wherein R1, R3, and A are as indicated above in claim 1, n=0 and R2 represents a 1,2,3,6-tetrahydropyridin-4-yl radical substituted in position 1 with an R1 radical.
7 Process for preparation of physiologically acceptable salts of the compounds with the general formula (I), according to claim 1, consisting in making react a compound with the general formula (I) with a mineral acid or an organic acid in a suitable solvent
8 Pharmaceutical compositions, characterised in that they contain. in addition to the pharmaceutically acceptable excipients, at least one compound with the general formula (I) or one of its physiologically acceptable salts, according to claims 1 and 2.
9 Compound according to claim 1 for prevention or treatment of anxiety, depression, cognitive memory disorders and senile dementia processes and other dementias where a cognition deficit is predominant, psychosis, infant hyperkinesia (ADHD, attention deficit/hyperactivity disorder) and other disorders mediated by the 5-HT6 receptor of serotonin in mammals, including man
10 Use of a compound derived of sulphonamide with the general formula (1),
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- wherein
- A represents a substituent selected from among
- A heteroaromatic ring of 5 or 6 members containing 1 or 2 heteroatoms selected from among oxygen, nitrogen and sulphur, optionally substituted by 1 or 2 halogen atoms, by a C1-C4 alkyl radical or by a phenyl or heteroaryl radical with 5 or 6 members containing 1 or 2 atoms of oxygen, nitrogen or sulphur;
- A bicyclic heteroaromatic ring containing 1 to 3 heteroatoms selected from among oxygen, nitrogen and sulphur, optionally substituted by 1 or 2 halogen atoms or by a C1-C4 alkyl radical,
- A group selected from among
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- R1 represents hydrogen, a C1-C4 alkyl radical or a benzyl radical;
- n represents 0, 1, 2. 3 or 4,
- R2 represents —NR4R5 or a group with formula.
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- Wherein the dotted line represents an optional chemical bond;
- R3, R4 y R5 independently represent hydrogen or a C1-C4 alkyl,
- X, Y and Z independently represent hydrogen, fluorine, chlorine, bromine, a C1-C4 alkyl. a C1-C4,alkoxy, a C1-C4 alkylthio. trifluoromethyl, cyano, nitro and —NR4R5,
- W represents a bond between the two rings, CH2, O, S and NR4,
- m represents 0, 1, 2, 3 or 4,
- or one of its physiologically acceptable salts,
- in the preparation of a medicament for preventing or treating anxiety, depression, cognitive memory disorders and senile dementia processes and other dementias where a cognition deficit is predominant. psychosis, infant hyperkinesia (ADHD, attention deficit/hyperactivity disorder) and other disorders mediated by the 5-HT6 receptor of serotonin in mammals, including man.
Dependencies are inferred from the claim text.