Patent EA-001919-B1 (EA)
Title: Sulphonamide derivatives
Inventor: ARNOLD MACKLIN B
IPC: A61K31/4245
Filed: 1998-01-30
Abstract: 1. A use of a compound of formula R<1>-L-NHSO2R<2>              I in which R<1> represents an unsubstituted or substituted aromatic or heteroaromatic group; R<2> represents (C1-C6)-alkyl, (C3-C6)-cycloalkyl, (C1-C6)-fluoroalkyl, (C1-C6)-chloroalkyl, (C2-C6)-alkenyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, phenyl which is unsubstituted or substituted by halogen, (C1-C4)-alkyl or (C1-C4)-alkoxy, or a group of formula R<3>R<4>N in which R<3> and R<4> each independently represents (C1-C4)-alkyl or, together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl, morpholino-, piperazinyl, hexahydroazepinyl or octahydroazocinyl group; and L represents a (C2-C4)-alkylene chain which is unsubstituted or substituted by one or two substituents selected independently from (C1-C6)-alkyl, aryl-(C1-C6)-alkyl, (C2-C6)-alkenyl, aryl-(C2-C6)-alkenyl and aryl, or by two substituents which, together with the carbon atom or carbon atoms to which they are attached form a (C3-C8)-carbocyclic ring; or a pharmaceutically acceptable salt thereof for obtaining a medicament for potentiating glutamate receptor function. 2. A method as claimed in Claim 1, in which R<2> represents (C1-C6)-alkyl, (C1-C6)-fluoroalkyl, (C2-C6)-alkenyl, or a group of formula R<3>R<4>N in which R<3> and R<4> each independently represents (C1-C4)-alkyl or, together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl, morpholino-, piperazinyl, hexahydroazepinyl or octahydroazocinyl group. 3. A method as claimed in Claim 1,2 in which L represents a group of formula   in which two substituents of R<5>, R<6>, R<7> and R<8> represents hydrogen and the remainder represent independently hydrogen, (C1-C6)-alkyl, aryl-(C1-C6)-alkyl, (C2-C6)-alkenyl, aryl-(C2-C6)-alkenyl or aryl, or together with the carbon atom or carbon atoms to which they are attached form a (C3-C8)-carbocyclic ring. 4. A method as claimed in Claim 3, in which R<6> and R<7> represent hydrogen, and R<5> and R<8> each independently represents hydrogen or (C1-C4)-alkyl, or together with the carbon atom to which they are attached form a (C3-C8)-carbocyclic ring. 5. A method as claimed in Claim 4, in which R<8> represents (C1-C4)-alkyl or R<5> and R<8> together with the carbon atom to which they are attached form a cyclopropyl ring. 6. A method as claimed in any of Claims 1-5, in which R<2> represents methyl, ethyl, propyl, 2-propyl, butyl, 2-methylpropyl, cyclohexyl, trifluoromethyl, 2,2,2-trifluoroethyl, chloromethyl, ethenyl, prop-2-enyl, methoxyethyl, phenyl, 4-fluorophenyl, or dimethylamino. 7. A method as claimed in Claim 6, in which R<2> represents ethyl, 2-propyl or dimethylamino. 8. A method as claimed in any of Claims 1-7, in which R<1> represents a naphthyl group or a phenyl, furyl, thienyl or pyridyl group which is unsubstituted or substituted by one or two substituents selected independently from halogen; nitro; cyano; hydroxyimino; (C1-C10)-alkyl; (C2-C10)-alkenyl; (C2-C10)-alkynyl; (C3-C8)-cycloalkyl; hydroxy-(C3-C8)-cycloalkyl; oxo-(C3-C8)-cycloalkyl; halo-(C1-C10)-alkyl; (CH2)yX<1>R<9> in which y is 0 or an integer of from 1 to 4, X<1> represents O, S, NR<10>, CO, COO, OCO, CONR<11>, NR<12>CO, NR<12>COCOO or OCONR<13>, R<9> represents hydrogen, (C1-C10)-alkyl, (C3-C10)-alkenyl, (C3-C10)-alkynyl, pyrrolidinyl, tetrahydrofuryl, morpholino or (C3-C8)-cycloalkyl and R<10>, R<11>, R<12> and R<13> each independently represents hydrogen or (C1-C10)-alkyl, or R<9> and R<10>, R<11>, R<12> or R<13> together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl or morpholino group; N-(C1-C4)-alkylpiperazinyl; N-phenyl-(C1-C4)-alkylpiperazinyl; thienyl; furyl; oxazolyl; isoxazolyl; pyrazolyl; imidazolyl; thiazolyl; pyridyl; pyridazinyl; pyrimidinyl; dihydrothienyl; dihydrofuryl; dihydrothiopyranyl; dihydropyranyl; dihydrothiazolyl; (C1-C4)-alkoxycarbonyldihydrothiazolyl; (C1-C4)-alkoxycarbonyldimethyldihydrothiazolyl; tetrahydrothienyl; tetrahydrofuryl; tetrahydrothiopyranyl; tetrahydropyranyl; indolyl; benzofuryl; benzothienyl; benzimidazolyl; and a group of formula R<14>-(L<a>)n-X<2>-(L<b>)m in which X<2> represents a bond, O, NH, S, SO, SO2, CO, CH(OH), CONH, NHCO, NHCONH, NHCOO, COCONH, OCH2CONH or CH=CH, L<a> and L<b> each represent (C1-C4)-alkylene, one of n and m is 0 or 1 and the other is 0, and R<14> represents a phenyl or heteroaromatic group which is unsubstituted or substituted by one or two of substituents selected from halogen, nitro, cyano, hydroxyimino, (C1-C10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-alkynyl, (C3-C8)-cycloalkyl, 4-(1,1-dioxotetrahydro-1,2-thiazinyl), halo-(C1-C10)-alkyl, cyano-(C2-C10)-alkenyl, phenyl, and (CH2)zX<3>R<15> in which z is 0 or an integer of from 1 to 4, X<3> represents O, S, NR<16>, CO, CH(OH), COO, OCO, CONR<17>, NR<18>CO, NHSO2, NHSO2NR<17>, NHCONH, OCONR<19> or NR<19>COO, R<15> represents hydrogen, (C1-C10)-alkyl, phenyl-(C1-C4)-alkyl, (C1-C10)-haloalkyl, (C1-C4)-alkoxycarbonyl-(C1-C4)-alkyl, (C1-C4)-alkylsulfonylamino-(C1-C4)-alkyl, (N-(C1-C4)-alkoxycarbonyl)-(C1-C4)-alkylsulfonylamino-(C1-C4)-alkyl, (C3-C10)-alkenyl, (C3-C10)-alkynyl, (C3-C8)-cycloalkyl, camphoryl or an aromatic or heteroaromatic group is unsubstituted or substituted by one or two of substituents selected from halogen, (C1-C4)-alkyl, halo-(C1-C4)-alkyl, di-(C1-C4)-alkylamino and (C1-C4)-alkoxy and R<16>, R<17>, R<18> and R<19> each independently represents hydrogen or (C1-C10)-alkyl, or R<15> and R<16>, R<17>, R<18> or R<19> together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl or morpholino group. 9. A method as claimed in any of Claims 1-8, in which R<1> represents a naphthyl group or a phenyl group which is unsubstituted or substituted by one or two substituents selected independently from halogen; nitro; cyano; (C1-C10)-alkyl; (C2-C10)-alkenyl; (C2-C10)-alkynyl; (C3-C8)-cycloalkyl; halo-(C1-C10)-alkyl; (CH2)yX<1>R<9> in which y is 0 or an integer of from 1 to 4, X<1> represents O, S, NR<10>, CO, COO, OCO, CONR<11>, NR<12>CO, OCONR<13>, R<9> represents hydrogen, (C1-C10)-alkyl, (C3-C10)-alkenyl, (C3-C10)-alkynyl or (C3-C8)-cycloalkyl and R<10>, R<11>, R<12> and R<13> each independently represents hydrogen or (C1-C10)-alkyl, or R<9> and R<10>, R<11>, R<12> or R<13> together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl or morpholino group; thienyl; furyl; oxazolyl; isoxazolyl; pyrazolyl; imidazolyl; thiazolyl; pyridyl; pyridazinyl; pyrimidinyl; dihydrothienyl; dihydrofuryl; dihydrothiopyranyl; dihydropyranyl; tetrahydrothienyl; tetrahydrofuryl; tetrahydrothiopyranyl; tetrahydropyranyl; indolyl; benzofuryl; benzothienyl; benzimidazolyl; and a group of formula R<14>-(L<a>)n-X<2>-(L<b>)m in which X<2> represents a bond, O, NH, S, SO, SO2, CO, CONH or NHCO, L<a> and L<b> each represent (C1-C4)-alkylene, one of n and m is 0 or 1 and the other is 0, and R<14> represents a phenyl group which is unsubstituted or substituted by one or two of substituents selected from halogen, nitro, cyano, (C1-C10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-alkynyl, (C3-C8)-cycloalkyl, halo-(C1-C10)-alkyl, and (CH2)zX<3>R<15> in which z is 0 or an integer of from 1 to 4, X<3> represents O, S, NR<16>, CO, COO, OCO, CONR<17>, NR<18>CO, OCONR<19>, R<15> represents hydrogen, (C1-C10)-alkyl, (C3-C10)-alkenyl, (C3-C10)-alkynyl or (C3-C8)-cycloalkyl and R<16>, R<17>, R<18> and R<19> each independently represents hydrogen or (C1-C10)-alkyl, or R<15> and R<16>, R<17>, R<18> or R<19> together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl or morpholino group. 10. A method as claimed in Claim 8 in which R<1> represents 2-naphthyl or a group of formula   in which R<20> represents halogen; nitro; cyano; hydroxyimino; (C1-C10)-alkyl; (C2-C10)-alkenyl; (C2-C10)-alkynyl; (C3-C8)-cycloalkyl; hydroxy-(C3-C8)-cycloalkyl; oxo-(C3-C8)-cycloalkyl; halo-(C1-C10)-alkyl; (CH2)yX<1>R<9> in which y is 0 or an integer of from 1 to 4, X<1> represents O, S, NR<10>, CO, COO, OCO, CONR<11>, NR<12>CO, NR<12>COCOO or OCONR<13>, R<9> represents hydrogen, (C1-C10)-alkyl, (C3-C10)-alkenyl, (C3-C10)-alkynyl, pyrrolidinyl, tetrahydrofuryl, morpholino or (C3-C8)-cycloalkyl and R<10>, R<11>, R<12> and R<13> each independently represents hydrogen or (C1-C10)-alkyl, or R<9> and R<10>, R<11>, R<12> or R<13> together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl or morpholino group; N-(C1-C4)-alkylpiperazinyl; N-phenyl-(C1-C4)-alkylpiperazinyl; thienyl; furyl; oxazolyl; isoxazolyl; pyrazolyl; imidazolyl; thiazolyl; pyridyl; pyridazinyl; pyrimidinyl; dihydrothienyl; dihydrofuryl; dihydrothiopyranyl; dihydropyranyl; dihydrothiazolyl; (C1-C4)-alkoxycarbonyldihydrothiazolyl; (C1-C4)-alkoxycarbonyldimethyldihydrothiazolyl; tetrahydrothienyl; tetrahydrofuryl; tetrahydrothiopyranyl; tetrahydropyranyl; indolyl; benzofuryl; benzothienyl; benzimidazolyl; and a group of formula R<14>-(L<a>)n-X<2>-(L<b>)m in which X<2> represents a bond, O, NH, S, SO, SO2, CO, CH(OH), CONH, NHCO, NHCONH, NHCOO, COCONH, OCH2CONH or CH=CH, L<a> and L<b> each represent (C1-C4)-alkylene, one of n and m is 0 or 1 and the other is 0, and R<14> represents a phenyl or heteroaromatic group which is unsubstituted or substituted by one or two of halogen; nitro; cyano; hydroxyimino, (C1-C10)-alkyl; (C2-C10)-alkenyl; (C2-C10)-alkynyl; (C3-C8)-cycloalkyl; 4-(1,1-dioxotetrahydro-1,2-thiazinyl), halo-(C1-C10)-alkyl; cyano-(C2-C10)-alkenyl, phenyl, (CH2)zX<3>R<15> in which z is 0 or an integer of from 1 to 4, X<3> represents O, S, NR<16>, CO, CH(OH), COO, OCO, CONR<17>, NR<18>CO, NHSO2, NHSO2NR<17>, NHCONH, OCONR<19> or NR<19>COO, R<15> represents hydrogen, (C1-C10)-alkyl, phenyl-(C1-C4)-alkyl, (C1-C10)-haloalkyl, (C1-C4)-alkoxycarbonyl-(C1-C4)-alkyl, (C1-C4)-alkylsulfonylamino-(C1-C4)-alkyl, (N-(C