RU2004127238A

RU2004127238A - BENZENESULPHANAMIDE DERIVATIVES AS ANTipsychotics

Info

Publication number: RU2004127238A
Application number: RU2004127238/04A
Authority: RU
Inventors: Стивен Марк БРОМИДЖ (IT); Стивен Марк Бромидж; Дэвид Гвин КУПЕР (GB); Дэвид Гвин КУПЕР; Йан Томсон ФОРБЗ (GB); Йан Томсон ФОРБЗ; Эндрю Деррик ГРИББЛ (GB); Эндрю Деррик ГРИББЛ; Кристофер Норберт ДЖОНСОН (GB); Кристофер Норберт Джонсон; Эндрю П ЛАЙТФУТ (GB); Эндрю П ЛАЙТФУТ; Стивен Фредерик МОСС (GB); Стивен Фредерик МОСС; Эндрю Х ПЕЙН (GB); Эндрю Х ПЕЙН; Шахзад Шарук РАХМАН (GB); Шахзад Шарук РАХМАН; Дэвид Р ВИТТИ (GB); Дэвид Р ВИТТИ
Original assignee: Глэксо Груп Лимитед (GB); Глэксо Груп Лимитед
Priority date: 2002-02-13
Filing date: 2003-02-13
Publication date: 2005-04-20

Claims

1. The compound of formula (I)

where A and B represent the groups - (CH ₂ ) _m - and - (CH ₂ ) _n - respectively;

R ¹ represents hydrogen or C _1-6 alkyl;

R ² represents hydrogen, halogen, hydroxy, cyano, nitro, hydroxy-C _1-6 -alkyl, trifluoromethyl, trifluoromethoxy, C _1-6 -alkyl, C _1-6 -alkoxy, C _1-6 -alkoxy-C _{1- 6-} alkyl, C _3-7 -cycloalkyl-C _1-6 -alkoxy, - (CH ₂ ) _p -C _3-6 -cycloalkyl, - (CH ₂ ) _p -C _3-6 -cycloalkyloxy, -CO-C _1-6 -alkyl, -SO ₂ -C _1-6 -alkyl, -SO-C _1-6 -alkyl, -S-С _1-6 -alkyl, C _1-6 -alkylsulfonyloxy, C _1-6 -sulfonyl -C _1-6 -alkyl, -CO ₂ -C _1-6 -alkyl, -CO ₂ NR ⁷ R ⁸ , -SO ₂ NR ⁷ R ⁸ , C _1-6 -alkylsulfonamido, C _1-6 -alkylsulfonamido-C _1-6 -alkyl, - (CH ₂ ) _p NR ⁷ R ⁸ , C _1-6 -alkylamido-C _1-6 -alkyl, - (CH ₂ ) _p NR ⁷ COR ⁸ , arylsulfonyl, arylsulfonyloxy, arylsulfonyl-C _{1 -6} -alkyl, arylsulfonamido, arylcarboxamido, arylsulfonamido-C _1-6 -alkyl, arylcarboxamido-C _1-6 -alkyl, aroyl, aroyl-C _1-6 -alkyl, aryl-C _1-6 -alkanoyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl, or a group CONR ⁷ R ⁸ or SO ₂ NR ⁷ R ⁸ where R ⁷ and R ⁸ together may be fused to form a 5-7 membered aromatic or non-aromatic heterocyclic ring optionally interrupted by an O or S atom ;

R ³ represents hydrogen or C _1-6 alkyl;

Ar represents an optionally substituted phenyl or an optionally substituted monocyclic heteroaryl group;

R ⁴ is optionally substituted aryl or optionally substituted heteroaryl;

R ⁷ and R ⁸ each independently represent hydrogen, C _1-6 alkyl, or together form a 5-7 membered heterocyclic ring;

Z represents a bond, an oxygen atom or a C _1-6 alkylene;

Y represents hydrogen or C _1-6 alkyl;

m and n are independently integers selected from 1 and 2;

p is independently an integer selected from 0, 1, 2, and 3;

q is an integer from 1 to 3;

r is an integer from 1 to 4;

or a pharmaceutically acceptable salt or solvate thereof.

2. The compound of formula (I), which is a

4- (4-chlorophenyl) -N- (2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) benzenesulfonamide;

4- (4-chlorophenyl) -N- (3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) benzenesulfonamide;

4- (4-chlorophenyl) -N-methyl-N- (2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) benzenesulfonamide;

4- (4-chlorophenyl) -N-methyl-N- (3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) benzenesulfonamide;

4- (3,4-dichlorophenyl) -N- (2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) benzenesulfonamide hydrochloride;

4- (4-chlorophenyl) -N- (8-methoxy-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) benzenesulfonamide hydrochloride;

4- (4-chlorophenyl) -N- (8-methoxy-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) benzenesulfonamide hydrochloride;

4- (4-chlorophenyl) -N- (1,2,3,4-tetrahydroisoquinolin-7-yl) benzenesulfonamide;

4- (4-chlorophenyl) -N- (2,3-dihydro-1H-isoindol-5-yl) benzenesulfonamide hydrochloride;

4- (4-chlorophenyl) -N- (2-methyl-2,3-dihydro-1H-isoindol-5-yl) benzenesulfonamide;

4- (4-chlorophenyl) -3-methyl-N- (2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) benzenesulfonamide hydrochloride;

4- (4-chlorophenyl) -3-methyl-N- (3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) benzenesulfonamide;

4- (4-chlorophenyl) -3-methyl-N- (8-methoxy-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) benzenesulfonamide hydrochloride;

4- (4-chlorophenyl) -3-methyl-N- (8-methoxy-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) benzenesulfonamide;

4- (5-chlorothiophen-2-yl) -N- (8-methoxy-3-methyl-2,3,4,5-tetrahydro-1H-benzo [d] azepin-7-yl) benzenesulfonamide;

4- (5-chlorothiophen-2-yl) -2-fluoro-N- (8-methoxy-3-methyl-2,3,4,5-tetrahydro-1H-benzo [d] azepin-7-yl) benzenesulfonamide ;

4- (4-chlorophenyl) -N- (8-dimethylamino-3-methyl-2,3,4,5-tetrahydro-1H-benzazepin-7-yl) benzenesulfonamide hydrochloride and

4- (4-fluorobenzyl) -N- (3-methyl-2,3,4,5-tetrahydro-1H-benzo [d] azepin-7-yl) benzenesulfonamide hydrochloride.

3. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 or 2, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier therefor.

4. The compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof according to claim 1 or 2, for use in treatment.

5. The compound of formula (I), or its pharmaceutically acceptable salt, or MES according to claim 1 or 2 for use in a condition in which modulation of the dopamine receptor is required.

6. The compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof according to claim 5, wherein the condition is selected from psychotic disorders, Parkinson's disease, substance abuse, dyskinetic disorders, depression, bipolar disorder, anxiety, cognitive impairment, disorders in relationships with food intake, obesity, sexual dysfunction, sleep disorders, vomiting, movement disorders, obsessive-compulsive disorders, amnesia, aggression, autism, vertigo, dementia, circadian rhythm disturbances and motor disorders functions of the stomach.

7. The use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof according to claim 1 or 2, for the manufacture of a medicament for the treatment of a condition in which dopamine receptor modulation is required.

8. The use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof according to claim 7, wherein the condition is selected from psychotic disorders, Parkinson's disease, substance abuse, dyskinetic disorders, depression, bipolar disorder, anxiety, cognitive impairment, disorders in connection with food intake, obesity, sexual dysfunction, sleep disorders, vomiting, movement disorders, obsessive-compulsive disorders, amnesia, aggression, autism, vertigo, dementia, circadian rhythm disturbances and disorders motor function of the stomach.

9. A method of treating a condition in which modulation of the dopamine receptor is required, comprising administering to a mammal in need of such treatment an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof according to claim 1 or 2.

10. The method of treating the condition of claim 9, wherein the condition is selected from psychotic disorders, Parkinson's disease, substance abuse, dyskinetic disorders, depression, bipolar disorder, anxiety, cognitive impairment, eating disorders, obesity, sexual dysfunction, disorders sleep, vomiting, movement disorders, obsessive-compulsive disorders, amnesia, aggression, autism, vertigo, dementia, circadian rhythm disturbances and disorders of the motor function of the stomach.