US 2003/0225084 A1Published application

Sulfonylguanidine compounds and pharmaceutical uses thereof

AssigneeGruenenthal GmbH

InventorsMatthias Gerlach, Heinz Uragg, Michael Haurand, Claudia Katharina Puetz, Corinna Maul, Boris Chizh

Life of this patent

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Abstract

Sulfonylguanidine compounds corresponding to the tautomeric formulas I and Ia, a method for producing them, pharmaceutical compositions containing them, and methods of using them to prepare medicaments and for treating various medical conditions. The sulfonylguanidine compounds have an affinity for the gabapentin binding site and can be used to treat conditions such as pain, epilepsy, migraine and others.

Claims24

Dependent claims

A method of treating a condition selected from:

the group consisting of pain, epilepsy and migraine;
or
the group consisting of hyperalgesia, allodynia, inflammatory pain and post-operative pain;
or
the group consisting of hot flashes, post-menopausal symptoms, amyotropic lateral sclerosis (ALS), reflex sympathetic dystrophy (RSD), spastic paralysis, restless leg syndrome, acquired nystagmus, psychiatric or neuropathological disorders, painful diabetic neuropathy, symptoms and pain due to multiple sclerosis or Parkinson's disease, neurodegenerative diseases, gastrointestinal lesions, erythromelalgic or post-poliomyelitic pain, and trigeminal or post-herpetic neuralgia;
or
a method of providing anticonvulsant, analgesic or anxiolytic treatment;
said method comprising administering to a patient in need thereof a pharmaceutically effective amount of a sulfonylguanidine compound corresponding to at least one of the tautomeric formulas I and Ia,
67
wherein
R1 is aryl or heteroaryl, that may be unsubstituted or singly or multiply substituted;
R2 is selected from the group consisting of:
C1-10-alkyl that is branched or unbranched, saturated or unsaturated, and singly or multiply substituted or unsubstituted;
C3-8-cycloalkyl that is saturated or unsaturated, and singly or multiply substituted or unsubstituted;
aryl or heteroaryl, that is unsubstituted or singly or multiply substituted;
aryl, C3-9-cycloalkyl and heteroaryl, that is bonded via saturated or unsaturated C1-3-alkyl, S(O)2 or NH, and that is unsubstituted or singly or multiply substituted;
NR4R5
where R4, R5 are independently selected from the group consisting of H;
C1-18-alkyl that is branched or unbranched, saturated or unsaturated, and singly or multiply substituted or unsubstituted;
C3-8-cycloalkyl that is saturated or unsaturated, and singly or multiply substituted or unsubstituted;
aryl or heteroaryl, that is unsubstituted or singly or multiply substituted;
or aryl, C3-9-cycloalkyl or heteroaryl, bonded via saturated or unsaturated C1-3-alkyl, and unsubstituted or singly or multiply substituted;
or
R4 and R5 together form —CH2CH2OCH2CH2—,
—CH2CH2N(R7) CH2CH2—, where R7 is selected from C1-18-alkyl that is branched or unbranched, saturated or unsaturated, and singly or multiply substituted or unsubstituted;
C3-8-cycloalkyl that is saturated or unsaturated, and singly or multiply substituted or unsubstituted;
aryl or heteroaryl, that is unsubstituted or singly or multiply substituted;
or
aryl, C3-9-cycloalkyl or heteroaryl, that is bonded via saturated or unsaturated C1-3-alkyl, and that is unsubstituted or singly or multiply substituted;
and
SO2R6
where R6 is selected from C1-18-alkyl that is branched or unbranched, saturated or unsaturated, and singly or multiply substituted or unsubstituted;
C3-8-cycloalkyl that is saturated or unsaturated, and singly or multiply substituted or unsubstituted;
aryl or heteroaryl, that is unsubstituted or singly or multiply substituted;
or aryl, C3-9-cycloalkyl or heteroaryl, that is bonded via saturated or unsaturated C1-3-alkyl, and that is unsubstituted or singly or multiply substituted;
R3 is H or CH3;
or
R2 and R3 together form
—CH2(CH2)nCH2—, where n=2 or 3, —CH2CH2OCH2CH2—, or —CH2CH2N(R8)CH2CH2
where R8 is C1-18-alkyl that is branched or unbranched, saturated or unsaturated, and singly or multiply substituted or unsubstituted;
optionally in the form of a racemate, a pure stereoisomer, enantiomer or diastereomer, or a mixture of stereoisomers, enantiomers or diastereomers;
in the form of a free acid or free base or a physiologically compatible salt, or in the form of a solvate, or a hydrate;
in both tautomeric forms corresponding to formulas I and Ia, or exclusively in one of the tautomeric forms corresponding to formula I or Ia, or in a mixture of the tautomeric forms corresponding to formulas I and Ia.

40 more elements

A sulfonylguanidine compound selected from the group consisting of:

N-{amino-[pyridin-2-yl-methyl)-amino]-methylene}-4-methylbenzenesulfonamide (1)
N-[amino-(benzylaminomethylene)]-4-methylbenzene-sulfonamide (2)
N-[(amino-4-methoxybenzylamino)-methylene]-4-methylbenzene-sulfonamide (6)
N-[aminophenethylaminomethylene]-4-methylbenzene-sulfonamide (14)
N-{amino-[(pyridin-2-yl-methyl)-amino]-methylene}-4-chlorobenzenesulfonamide (21)
N-{amino-[(pyridin-4-yl-methyl)-amino]-methylene}-4-methylbenzenesulfonamide (22)
N-{amino-[(pyridin-3-yl-methyl)-amino]-methylene}-4-methylbenzenesulfonamide (23)
N-{amino[(pyridin-2-yl-methyl)-amino]-methylene}-4-bromobenzenesulfonamide (32)
N-{amino[(pyridin-2-yl-methyl)-amino]-methylene}-3,4-dichlorobenzenesulfonamide (33)
N-{amino[(pyridin-2-yl-methyl)-amino]-methylene}-4-isopropylbenzenesulfonamide (34)
N-{amino[(pyridin-2-yl-methyl)-amino]-methylene}-4-iodobenzenesulfonamide (35)
N-{amino[(pyridin-2-yl-methyl)-amino]-methylene}-benzenesulfonamide (36)
Naphthalene-2-sulfonic acid amino-[(pyridin-2-yl-methyl)-amino]-methylene amide (37)
1-methyl-1H-imidazole-4-sulfonic acid amino-[(pyridin-2-yl-methyl)-amino]-methylene amide (38)
N-[4-({amino-[(pyridin-2-yl-methyl)-amino]-methylene}-sulfamoyl)-phenyl]-acetamide (39)
N-{amino[(pyridin-2-yl-methyl)-amino]-methylene}-4-fluorobenzenesulfonamide (40)
N-{amino[(pyridin-2-yl-methyl)-amino]-methylene}-2,4,6-trimethylbenzenesulfonamide (41)
N-{amino[(pyridin-2-yl-methyl)-amino]-methylene}-4-propylbenzenesulfonamide (42)
N-{amino[(pyridin-2-yl-methyl)-amino]-methylene}-4-methoxybenzenesulfonamide (43)
Naphthalene-1-sulfonic acid amino-[(pyridin-2-yl-methyl)-amino]-methylene amide (44)
N-{amino[(pyridin-2-yl-methyl)-amino]-methylene}-3-methylbenzenesulfonamide (45)
Thiophene-2-sulfonic acid amino-[(pyridin-2-yl-methyl)-amino]-methylene amide (46)
Quinoline-8-sulfonic acid amino-[(pyridin-2-yl-methyl)-amino]-methylene amide (47)
5-chloro-3-methylbenzo[b]thiophene-2-sulfonic acid amino-[(pyridin-2-yl-methyl)-amino]-methylene amide (48)
N-{amino[(pyridin-2-yl-methyl)-amino]-methylene}-4-tert.-butylbenzenesulfonamide (49)
N-{amino[(pyridin-2-yl-methyl)-amino]-methylene}-4-butylbenzenesulfonamide (50)
N-{amino[(pyrimidin-2-yl-methyl)-amino]-methylene}-4-tert.-butylbenzenesulfonamide (51)
N-{amino[(furan-2-yl-methyl)-amino]-methylene}-4-butylbenzenesulfonamide (52)
N-{amino[(furan-2-yl-methyl)-amino]-methylene}-4-methylbenzenesulfonamide (53)
N-{amino[(furan-2-yl-methyl)-amino]-methylene}-4-isopropylbenzenesulfonamide (54)
N-{amino[(furan-2-yl-methyl)-amino]-methylene}-4-propylbenzenesulfonamide (55)
N-{amino[(furan-2-yl-methyl)-amino]-methylene}-4-tert.-butylbenzenesulfonamide (56)
N-{amino[(thiophen-2-yl-methyl)-amino]-methylene}-4-butylbenzenesulfonamide (57)
N-{amino[(thiophen-2-yl-methyl)-amino]-methylene}-4-propylbenzenesulfonamide (58)
N-{amino[(thiophen-2-yl-methyl)-amino]-methylene}-4-isopropylbenzenesulfonamide (59)
N-{amino[(thiophen-2-yl-methyl)-amino]-methylene}-4-tert.-butylbenzenesulfonamide (60)
N-{amino[(thiophen-2-yl-methyl)-amino]-methylene}-4-chlorobenzenesulfonamide (61)
N-{amino[(thiophen-2-yl-methyl)-amino]-methylene}-4-methylbenzenesulfonamide (62), and
N-{amino[(furan-2-yl-methyl)-amino]-methylene}-4-chlorobenzenesulfonamide (63),
optionally in the form of their racemates, their pure stereoisomers, in particular enantiomers or diastereomers, or in the form of mixtures of the stereoisomers, in particular of the enantiomers or diastereomers, in an arbitrary mixture ratio;
in the represented form or in the form of their acids or their bases;
or in the form of their salts, in particular the physiologically compatible salts, preferably the hydrochloride or sodium salt;
or in the form of their solvates, in particular the hydrates;
in both tautomeric forms according to formulas I and Ia, exclusively in one of the tautomeric forms according to formulas I or Ia or also in mixtures of both forms according to formulas I and Ia.

41 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/402,382Filed 31 Mar 2003
Priority: DE 100 48 716.530 Sep 2000
Published: 4 Dec 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification34 codes

C07D 213/40
Radicals substituted by singly-bound nitrogen atoms: acylated substituent nitrogen atom
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 15/12
Drugs for genital or sexual disorders ; Contraceptives: for climacteric disorders

Family

Application10/402,382Continuation · filed 31 Mar 2003
US 2003/0225084 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A method of treating a condition selected from:

the group consisting of pain, epilepsy and migraine;
or
the group consisting of hyperalgesia, allodynia, inflammatory pain and post-operative pain;
or
the group consisting of hot flashes, post-menopausal symptoms, amyotropic lateral sclerosis (ALS), reflex sympathetic dystrophy (RSD), spastic paralysis, restless leg syndrome, acquired nystagmus, psychiatric or neuropathological disorders, painful diabetic neuropathy, symptoms and pain due to multiple sclerosis or Parkinson's disease, neurodegenerative diseases, gastrointestinal lesions, erythromelalgic or post-poliomyelitic pain, and trigeminal or post-herpetic neuralgia;
or
a method of providing anticonvulsant, analgesic or anxiolytic treatment;
said method comprising administering to a patient in need thereof a pharmaceutically effective amount of a sulfonylguanidine compound corresponding to at least one of the tautomeric formulas I and Ia,
67
wherein
R1 is aryl or heteroaryl, that may be unsubstituted or singly or multiply substituted;
R2 is selected from the group consisting of:
C1-10-alkyl that is branched or unbranched, saturated or unsaturated, and singly or multiply substituted or unsubstituted;
C3-8-cycloalkyl that is saturated or unsaturated, and singly or multiply substituted or unsubstituted;
aryl or heteroaryl, that is unsubstituted or singly or multiply substituted;
aryl, C3-9-cycloalkyl and heteroaryl, that is bonded via saturated or unsaturated C1-3-alkyl, S(O)2 or NH, and that is unsubstituted or singly or multiply substituted;
NR4R5
where R4, R5 are independently selected from the group consisting of H;
C1-18-alkyl that is branched or unbranched, saturated or unsaturated, and singly or multiply substituted or unsubstituted;
C3-8-cycloalkyl that is saturated or unsaturated, and singly or multiply substituted or unsubstituted;
aryl or heteroaryl, that is unsubstituted or singly or multiply substituted;
or aryl, C3-9-cycloalkyl or heteroaryl, bonded via saturated or unsaturated C1-3-alkyl, and unsubstituted or singly or multiply substituted;
or
R4 and R5 together form —CH2CH2OCH2CH2—,
—CH2CH2N(R7) CH2CH2—, where R7 is selected from C1-18-alkyl that is branched or unbranched, saturated or unsaturated, and singly or multiply substituted or unsubstituted;
C3-8-cycloalkyl that is saturated or unsaturated, and singly or multiply substituted or unsubstituted;
aryl or heteroaryl, that is unsubstituted or singly or multiply substituted;
or
aryl, C3-9-cycloalkyl or heteroaryl, that is bonded via saturated or unsaturated C1-3-alkyl, and that is unsubstituted or singly or multiply substituted;
and
SO2R6
where R6 is selected from C1-18-alkyl that is branched or unbranched, saturated or unsaturated, and singly or multiply substituted or unsubstituted;
C3-8-cycloalkyl that is saturated or unsaturated, and singly or multiply substituted or unsubstituted;
aryl or heteroaryl, that is unsubstituted or singly or multiply substituted;
or aryl, C3-9-cycloalkyl or heteroaryl, that is bonded via saturated or unsaturated C1-3-alkyl, and that is unsubstituted or singly or multiply substituted;
R3 is H or CH3;
or
R2 and R3 together form
—CH2(CH2)nCH2—, where n=2 or 3, —CH2CH2OCH2CH2—, or —CH2CH2N(R8)CH2CH2
where R8 is C1-18-alkyl that is branched or unbranched, saturated or unsaturated, and singly or multiply substituted or unsubstituted;
optionally in the form of a racemate, a pure stereoisomer, enantiomer or diastereomer, or a mixture of stereoisomers, enantiomers or diastereomers;
in the form of a free acid or free base or a physiologically compatible salt, or in the form of a solvate, or a hydrate;
in both tautomeric forms corresponding to formulas I and Ia, or exclusively in one of the tautomeric forms corresponding to formula I or Ia, or in a mixture of the tautomeric forms corresponding to formulas I and Ia.

40 more elements

Facts

Application

10/402,382Filed 31 Mar 2003

Priority

DE 100 48 716.530 Sep 2000

Published

4 Dec 2003

Term ends

Not estimatedThe source records don’t support an estimate.

Classification34 codes

C07D 213/40
Radicals substituted by singly-bound nitrogen atoms: acylated substituent nitrogen atom
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 15/12
Drugs for genital or sexual disorders ; Contraceptives: for climacteric disorders