Patent EA-002351-B1 (EA)
Title: Sulphonamide derivatives, process for their preparation, and their use as medicaments
Inventor: BROMIDGE STEVEN MARK
IPC: C07D261/10
Filed: 1997-12-15
Abstract: 1. A compound of formula (I) or a salt thereof:   (I) wherein: P is phenyl, naphthyl, benzothiazolyl, benzothiadiazolyl, benzothiophenyl, quinolyl, izoxazolyl, benzofuranyl or indolyl. A is a single bond, a C1-6 alkylene or a C1-6 alkenylene group; R<1> is halogen, C1-6 alkyl optionally substituted by one or more halogen atoms, C3-6 cycloalkyl, CO C1-6 alkyl, C1-6 alkoxy, OCF3, hydroxy, hydroxy C1-6 alkyl, hydroxy C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, nitro, amino, alkylamino or dialkylamino, cyano or R<1> is phenyl, naphthyl or pyridyl, n is 0, 1, 2, 3, 4, 5 or 6: R<2> is hydrogen, C1-6 alkyl or aryl C1-6 alkyl; R<3> is a group R<5> or together with R<5> forms a group (CH2)2O or (CH2)3O or R<3> is linked to R<2> to form a group (CH2)2O or (CH2)3O; R<4> is a N-piperazine ring optionally substituted by C1-6 alkyl, R<5> is hydrogen, halogen, C1-6 alkyl, C3-6 cycloalkyl, COC1-6 alkyl, C1-6 alkoxy, hydroxy, hydroxy C1-6 alkyl, hydroxy C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, nitro, trifluoromethyl, cyano or aryl. 2. A compound according to claim 1 in which P is phenyl, thiophene, benzothiophene or naphthyl. 3. A compound according to claim 1 or 2 in which R<1> is halogen or C1-6 alkyl optionally substituted by one or more halogen atoms. 4. A compound according to any one of claims 1 to 3 in which R<2> is hydrogen. 5. A compound according to any one of claims 1 to 4 in which R<4> is an optionally substituted piperazine ring. 6. A compound according to any one of claims 1 to 5 in which R<5> is C1-6 alkoxy. 7. A compound according to any one of claims 1 to 6 in which R<5> is para with respect to the sulphonamide linkage. 8. A compound according to any one of claims 1 to 7 in which P-A is 5-chloro-3methyl-benzo [2]thiophen-2-yl. 9. A compound according to claim 1 which is: 4-Bromo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide, N-[4-Methoxy-3-(4-methylpiperazin 1-yl)phenyl]-2-thiophenesulfonamide, N-[4-Methoxy-3-(4-methylpiperazin-1-yl)phenyl]-5-(pyridin-2-yl)-2-thiophenesulfonamide, 2,5-Dichloro-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-thiophenesulfonamide, 4-Bromo-5-chloro-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2-thiophenesulfonamide, N-[4-Methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide, 3 -Bromo-5-chloro-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2-thiophenesulfonamide, N-[4-Methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzylsulfonamide, 2-Bromo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide, 3-Bromo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide, 3-Chloro-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-4-methylbenzenesulfonamide, N-[4-Methoxy-3-(4-methylpiperazin-1-yl)phenyl]-trans-styrenesulfonamide, 3,4-Dichloro-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide, 3,5-Dichloro-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide, N-[4-Methoxy-3-(4-methylpiperazin-1-yl)phenyl]-[2,1,3]benzothiadizole-4sulfonamide, 5-Chloro-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-methyl-2benzothiophenesulfonamide, N-[4-Methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2-methyl-5-nitro-benzenesulfonamide, N-[4-Methoxy-3-(4-methylpiperazin-1-yl) phenyl]-2-trifluoromethylbenzenesulfonamide, N-[4-Methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-trifluoromethyl- benzenesulfonamide, 2,3-Dichloro-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-benzenesulfonamide, 5-Iodo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2-methylbenzenesulfonamide, 3-Iodo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide, 3-Iodo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-4-methyl-benzenesulfonamide, 5-Chloronaphthalene-2-sulfonic acid[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl] amide, 5-Chloronaphthalene-1-sulfonic acid[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl] amide, 4-Chloronaphthalene-1-sulfonic acid[4-methoxy-3-(4-methylpiperazin-1-yl) phenyl] amide, 7-Chloronaphthalene-1-sulfonic acid[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]amide, 5-Chloro-2-methylbenzo [b]thiophene-3-sulfonic acid [4-methoxy-3-(4-methylpiperazin-1-yl)phenyl] amide, Benzofuran-2-sulfonic acid [4-methoxy-3-(4-methylpiperazin-1-yl)phenyl] amide, 1-Methyl-1-H-indole-2-sulfonic acid [4-methoxy-3-(4-methylpiperazin-1-yl)phenyl] amide, 5-Pyridin-2-ylthiophene-2-sulfonic acid (4-methoxy-3-piperazin-1-ylphenyl) amide, N-(4-Methoxy-3-piperazin-1-ylphenyl)-3-trifluoromethylbenzenesulfonamide, 3-Iodo-N-(4-methoxy-3-piperazin-1-ylphenyl)benzenesulfonamide, 3,5-Dimethylisoxazole-4-sulfonic acid (4-methoxy-3-piperazin-1-ylphenyl) amide, 3,5-Dichloro-N-(4-methoxy-3-piperazin-1-ylphenyl)benzenesulfonamide, 2,5 -Dibromo-3,6-difluoro-N-(4-methoxy-3-piperazin-1-ylphenyl)benzenesulfonamide, Naphthalene-1-sulfonic acid (4-methoxy-3-piperazin-1-ylphenyl) amide, 2-Bromo-5-chlorothiophene-2-sulfonic acid (4-methoxy-3-piperazin-1-ylphenyl) amide, 2-Chloro-4-fluoro-N-(4-methoxy-3 -piperazin-1-ylphenyl)benzenesulfonamide, 3-Bromo-N-(4-methoxy-3-piperazin-1-ylphenyl)benzenesulfonamide, 3-Chloro-N-(4-methoxy-3-piperazin-1-ylphenyl)benzenesulfonamide, 5-Chloronaphthalene-2-sulfonic acid (4-methoxy-3-piperazin-1-ylphenyl)amide, 4-Bromo-5-chlorothiophene-2-sulfonic acid (4-methoxy-3-piperazin-1-ylphenyl) amide, 2,5-Dichlorothiophene-3-sulfonic acid (4-methoxy-3-piperazin-1-ylphenyl) amide 4-Bromo-N-(4-methoxy-3-piperazin-1-ylphenyl)benzenesulfonamide, 5-Chloro-3-methylbenzo[b]thiophene-2-sulfonic acid (4-methoxy- 3-piperazin- 1 - ylphenyl) amide, 5 -Chloro-2-methylbenzo [b]thiophene-3 -sulfonic acid (4-methoxy-3 -piperazin-l- ylphenyl) amide, 1-Methyl-1H-indole-2-sulfonic acid (4-methoxy-3 -piperazin- 1 -ylphenyl) amide, Benzofuran-2-sulfonic acid (4-methoxy-3-piperazin-1-ylphenyl) amide, Naphthalene-2-sulfonic acid(4-methoxy-3-piperazin- 1ylphenyl)amide, 5-Chloronaphthalene- 1-sulfonic acid(4-methoxy-3-piperazin- 1 -ylphenyl)amide, 4-Chloro-2,5 -dimethyl-N-(4-methoxy-3 -piperazin- 1 -ylphenyl)benzenesulfonamide, 3,4-Dichloro-N-(4-methoxy-3 -piperazin- 1 -ylphenyl)benzenesulfonamide, 3-Chloro-N-(4-methoxy-3 -piperazin- 1 -ylphenyl)-4-methyl-benzenesulfonamide, 2-Trifluoromethyl-N-(4-methoxy-3 -piperazin- 1 -ylphenyl)benzenesulfonamide, 4-Iodo-N-(4-methoxy-3 -piperazin- 1 -ylphenyl)benzenesulfonamide, 4-Tert-butyl-N-(4-methoxy-3-piperazin- 1 -ylphenyl)benzenesulfonamide, Naphthalene- 1 -sulfonic acid [7-(4-methylpiperazin- 1 -yl)-2,3 -dihydrobenzofuran-5 -yl] amide, Thiophene-2-sulfonic acid [7-(4-methylpiperazin- 1 -yl)-2,3-dihydrobenzofuran-5-yl] amide, 5-Chlorothiophene-2-sulfonic aicd [7-(4-methylpiperazin-1-yl)-2,3dihydrobenzofuran-5-yl] amide, 5-Pyridin-2-ylthiophene-2-sulfonic acid [7-(4-methylpiperazin- 1 -yl)-2, 3- dihydrobenzofuran-5-yl] amide, 2,5-Dichlorothiophene-3-sulfonic acid [7-(4-methylpiperazin-1-yl)-2,3dihydrobenzofuran-5-yl] amide, 4-Bromo-5-chlorothiophene-2-sulfonic acid [7-(4-methylpiperazin-1-yl)-2,3dihydrobenzofuran-5-yl] amide, 3-Bromo-5-chlorothiophene-2-sulfonic acid [7-(4-methylpiperazin-2-yl)-2,3dihydrobenzofuran-5-yl] amide, 4-Chloro-2,5-dimethyl-N-[7-(4-methylpiperazin-1-yl)-2,3-dihydrobenzofuran-5yl]benzenesulfonamide, 5-Chloro-3-methylbenzo[b]thiophene-2-sulfonic acid [7-(4-methylpiperazin-1-yl)-2,3dihydrobenzofuran-5-yl] amide, Naphthalene-2-sulfonic acid [7-(4-methylpiperazin-1-yl)-2,3-dihydrobenzofuran-5-yl] amide. 3-Bromo-N-[7-(4-methylpiperazin-1-yl)-2,3-dihydrobenzofuran-5-yl]benzenesulfonamide, 3,5-Dichloro-N-[7-(4-methylpiperazin-1-yl)-2,3-dihydrobenzofuran-5-yl]benzenesulfonamide, 4-Tert-Butyl-N-[7-(4-methylpiperazin-1-yl)-2,3-dihydrobenzofuran-5-yl]benzenesulfonamide, 2,5-Dibromo-3,6-difluoro-N-[7-(4-methylpiperazin-1-yl)-2,3-dihydrobenzofuran-5-yl]benzenesulfonamide, 2,5-Dibromo-3,6-difluoro-N-(7-piperazin-1-yl-2,3 -dihydrobenzofuran-5-yl)benzenesulfonamide, 4-Chloro-2,5-dimethyl-N-(7-piperazin-1-yl-2,3-dihydrobenzofuran-5-yl)benzenesulfonamide, 5-Chloro-3-methylbenzo[b]thiophene-2-sulphonic acid [3-(4-cyclopropylmethylpiperazin-1-yl)-4-methoxy-phenyl] amide 5-Chloro-3 -methylbenzo [b]thiophene-2-sulphonic acid [3-(4-benzyl-piperazin-1-yl)-4-methoxy-phenyl] -amide, 5 -Chloro-3 -methylbenzo [b]thiophene-2-sulphonic acid [4-hydroxy-3-(4-methylpiperazin-1-yl)-phenyl]-amide, 5-Chloro- 3-methyl-benzo [b]thiophene-2-sulphonic acid [4-benzyloxy-3-(4-methylpiperazin-1-yl)-phenyl]-amide, 5-Chloro-3-methylbenzo [b]thiophene-2-sulphonic acid [4-ethoxy-3-(4-methylpiperazin-1-yl)-phenyl]-amide, 5-Chloro-3-methylbenzo[b]thiophene-2-sulphonic acid [4-isopropoxy-3-(4-methylpiperazin-1-yl)-phenyl]-amide, Naphthalene-2-sulfonic acid [2-bromo-5-(4-methylpiperazin-1-yl)phenyl]amide, 5-Chloro-3-methylbenzo[b]thiophene-2-sulfonic acid [4-chloro-3-(4-methylpiperazin1-yl)phenyl]amide, Naphthalene-2-sulfonic acid [4-bromo-3-(4-methylpiperazin-1-yl)phenyl] amide, 1-(5-Chloro-3-methylbenzo[b]thiophene-2-sulfonyl)-6-(4-methylpiperazin-1-yl)-2,3dihydro-1H-indole, 1-(5 -Chloro-3-methylbenzo [b]thiophene-2-sulfonyl)-5-methoxy-6-(4methylpiperazin-1-yl)-2,3-dihydro- 1H-indole, 5-Chloro-3-methylbenzo[b]thiophene-2-sulfonic acid [4-methoxy-2-methyl-3-(4methylpiperazin-1-yl)phenyl] amide, 5-Chloro-3-methylbenzo[b]thiophene-2-sulfonic acid [2-(2-hydroxyethyl)-4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]amide, 1-(5-Chloro-3-methylbenzo[b]thiophene-2-sulfonyl)-5-methoxy-4-(4-methylpiperazin-1-yl)-2,3 -dihydro- 1 H-indole hydrochloride, 5-Chloro-3-methylbenzo[b]thiophene-2-sulfonic acid [3-methoxy-4-(4-methylpiperazin-1-yl)phenyl] amide, 5-Chloro-3-methylbenzo[b]thiophene-2-sulfonic acid [4-methoxy-3-(1-methylpyrrolidin-4-yl)-phenyl] -amide, Naphthalene-2-sulfonic acid [3-(4-methylpiperazin-1-yl) phenyl]amide, 2,3,4-Trichloro-N-(4-methoxy-3-piperazin-1-yl-phenyl) benzenesulfonamide, 2,3 -Dichloro-N-(4-methoxy-3 -piperazin-1-yl-phenyl) benzenesulfonamide, 3-Chloro-2-methyl-N-(4-methoxy-3-piperazin-1-yl-phenyl) benzenesulfonamide, 4-Chloro-N-(4-methoxy-3-piperazin-1-yl-phenyl) benzenesulfonamide, 5-Bromo-thiophene-2-sulfonic acid (4-methoxy-3-piperazin-1-yl-phenyl)-amide, 2,3-Dichloro-N-[4-methoxy