US 2002/0002158 A1 · Sulphonamide derivatives

Abstract

Glutamate receptor function in a mammal may be potentiated using an effective amount of a compound of formula R1—L—NHSO2R2 I in which R1 represents an unsubstituted or substituted aromatic or heteroaromatic group; R2 represents (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)fluoroalkyl, (1-6C)chloroalkyl, (2-6C)alkenyl, (1-4C)alkoxy(1-4C)alkyl, phenyl which is unsubstituted or substituted by halogen, (1-4C)alkyl or (1-4C)alkoxy, or a group, of formula R3R4N in which R3 and R4 each independently represents (1-4C)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 (2-4C)alkylene chain which is unsubstituted or substituted by one or two substituents selected independently from (1-6C)alkyl, aryl(1-6C)alkyl, (2-6C)alkenyl, aryl(2-6C)alkenyl and aryl, or by two substituents which, together with the carbon atom or carbon atoms to which they are attached form a (3-8C)carbocyclic ring; and pharmaceutically acceptable salts thereof. Also disclosed are novel compounds of formula I, processes for preparing them and pharmaceutical compositions containing them.

Claims27

Dependent claims

Use of a compound of formula

R1—L—NHSO2R2 I
in which
R1 represents an unsubstituted or substituted aromatic or heteroaromatic group;
R2 represents (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)fluoroalkyl, (1-6C)chloroalkyl, (2-6C)alkenyl, (1-4C)alkoxy(1-4C)alkyl, phenyl which is unsubstituted or substituted by halogen, (1-4C)alkyl or (1-4C)alkoxy, or a group of formula R3R4N in which R3 and R4 each independently represents (1-4C)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 (2-4C)alkylene chain which is unsubstituted or substituted by one or two substituents selected independently from (1-6C)alkyl, aryl(1-6C)alkyl, (2-6C)alkenyl, aryl(2-6C)alkenyl and aryl, or by two substituents which, together with the carbon atom or carbon atoms to which they are attached form a (3-8C)carbocyclic ring;
or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for potentiating glutamate receptor function:

4 more elements

A compound of the formula

7
in which
R1 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;
(1-10C)alkyl;
(2-10C)alkenyl;
(2-10C)alkynyl;
(3-8C)cycloalkyl;
hydroxy(3-8C)cycloalkyl;
oxo(3-8C)cycloalkyl;
halo(1-10C)alkyl;
(CH2)yX1R9 in which y is 0 or an integer of from 1 to 4, X1 represents O, S, NR10, CO, COO, OCO, CONR11, NR12CO, NR12COCOO or OCONR13, R9 represents hydrogen, (1-10C)alkyl, (3-10C)alkenyl, (3-10C)alkynyl, pyrrolidinyl, tetrahydrofuryl, morpholino or (3-8C)cycloalkyl and R10, R11, R12 and R13 each independently represents hydrogen or (1-10C)alkyl, or R9 and R10, R11, R12 or R13 together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl or morpholino group;
N-(1-4C)alkylpiperazinyl;
N-phenyl(1-4C)alkylpiperazinyl;
thienyl;
furyl;
oxazolyl;
isoxazolyl;
pyrazolyl;
imidazolyl;
thiazolyl;
pyridyl;
pyridazinyl;
pyrimidinyl;
dihydrothienyl;
dihydrofuryl;
dihydrothiopyranyl;
dihydropyranyl;
dihydrothiazolyl;
(1-4C)alkoxycarbonyldihydrothiazolyl;
(1-4C)alkoxycarbonyldimethyldihydrothiazolyl;
tetrahydrothienyl;
tetrahydrofuryl;
tetrahydrothiopyranyl;
tetrahydropyranyl;
indolyl;
benzofuryl;
benzothienyl;
benzimidazolyl;
and a group of formula R14—(La)n—X2—(Lb)m in which X2 represents a bond, O, NH, S, SO, SO2, CO, CH(OH), CONH, NHCO, NHCONH, NHCOO, COCONH, OCH2CONH or CH═CH, La and Lb each represent (1-4C)alkylene, one of n and m is 0 or 1 and the other is 0, and R14 represents a phenyl or heteroaromatic group which is unsubstituted or substituted by one or two of halogen, nitro, cyano, hydroxyimino, (1-10C) alkyl, (2-10C)alkenyl, (2-10C)alkynyl, (3-8C)cycloalkyl, 4-(1,1-dioxotetrahydro-1,2-thiazinyl), halo(1-10C)alkyl, cyano(2-10C)alkenyl, phenyl, and (CH2)zX3R15 in which z is 0 or an integer of from 1 to 4, X3 represents O, S, NR16, CO, CH(OH), COO, OCO, CONR17, NR18CO, NHSO2, NHSO2NR17, NHCONH, OCONR19 or NR19COO, R15 represents hydrogen, (1-10C)alkyl, phenyl(1-4C)alkyl, (1-10C)haloalkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, (1-4C)alkylsulfonylamino(1-4C)alkyl, (N-(1-4C)alkoxycarbonyl)(1-4C)alkylsulfonylamino(1-4C)alkyl, (3-10C)alkenyl, (3-10C)alkynyl, (3-8C)cycloalkyl, camphoryl or an aromatic or heteroaromatic group which is unsubstituted or substituted by one or two of halogen, (1-4C)alkyl and (1-4C)alkoxy and R16, R17, R18 and R19 each independently represents hydrogen or (1-10C)alkyl, or R15 and R16, R17, R18 or R19 together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl or morpholino group;
R2 represents (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)fluoroalkyl, (1-6C)chloroalkyl, (2-6C)alkenyl, (1-4C)alkoxy(1-4C)alkyl, phenyl which is unsubstituted or substituted by halogen, (1-4C)alkyl or (1-4C)alkoxy, or a group of formula R3R4N in which R3 and R4 each independently represents (1-4C)alkyl or, together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl, morpholino, piperazinyl, hexahydroazepinyl or octahydroazocinyl group;
and
either one of R5, R6, R7 and R8 represents (1-6C)alkyl;
aryl(1-6C)alkyl;
(2-6C)alkenyl;
aryl(2-6C)alkenyl or aryl, or two of R5, R6, R7 and R8 together with the carbon atom or carbon atoms to which they are attached form a (3-8C) carbocyclic ring;
and the remainder of R5, R6, R7 and R8 represent hydrogen;
or a pharmaceutically acceptable salt thereof, but excluding N-(2,2-diphenylethyl)methanesulphonamide and those compounds of formula I in which R7 represents methyl;
R5, R6 and R8 represent hydrogen;
and
(a) R1 represents phenyl and R2 represents methyl, butyl, fluoromethyl, difluoromethyl, trifluoromethyl, dimethylamino or piperidinyl;
or
(b) R1 represents 4-chlorophenyl, 4-nitrophenyl or 3-methoxyphenyl, and R2 represents methyl;
or
(c) R1 represents 4-nitrophenyl and R2 represents trifluoromethyl.

54 more elements

Dependencies are inferred from the claim text.

Sulphonamide derivatives

Life of this patent

Sulphonamide derivatives

Life of this patent

Abstract

Claims27