1,2- bis-sulfonamide derivatives as chemokine receptor modulators

Patent metadata

Field	Value
Publication number	US-9603834-B2
Application number	US-201514847934-A
Country	US
Kind code	B2
Filing date	Sep 8, 2015
Priority date	Dec 16, 2010
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

The present invention relates to novel bis-sulfonamide derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of chemokine receptors.

First claim

What is claimed is:

1. A method of treating a skin inflammatory disease or an ocular inflammatory disease, the method comprising administering to a subject in need thereof a compound having Formula I, Formula II, or Formula III:

or an enantiomer, a diastereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, wherein:
R 1 is H or substituted or unsubstituted C 1-6 alkyl;
R 2 is H or substituted or unsubstituted C 1-6 alkyl;
R 5 is substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C 3-8 cycloalkyl, substituted or unsubstituted C 3-8 cycloalkenyl or is substituted or unsubstituted C 6-10 aryl;
R 6 is 2-benzofuran, 2-thienyl, 5-chloro-2-thienyl, 4,5-dichloro-2-thienyl, 4-chloro-3-methylphenyl, or 4-chloro-3-trifluoromethylphenyl;
R 7 is H, substituted or unsubstituted C 1-6 alkyl, halogen, —OC 1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 9 , NR 10 R 11 or hydroxyl;
R 8 is H, substituted or unsubstituted C 1-6 alkyl, halogen, —OC 1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 12 , NR 13 R 14 or hydroxyl;
R 16 is H, substituted or unsubstituted C 1-6 alkyl, halogen, —OC 1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 19 , NR 20 R 21 or hydroxyl;
R 18 is H, substituted or unsubstituted C 1-6 alkyl, halogen, —OC 1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 22 , NR 23 R 24 or hydroxyl;
R 9 is H or substituted or unsubstituted C 1-6 alkyl;
R 10 is H or substituted or unsubstituted C 1-6 alkyl;
R 11 is H or substituted or unsubstituted C 1-6 alkyl;
R 12 is H or substituted or unsubstituted C 1-6 alkyl;
R 13 is H or substituted or unsubstituted C 1-6 alkyl;
R 14 is H or substituted or unsubstituted C 1-6 alkyl;
R 19 is H or substituted or unsubstituted C 1-6 alkyl;
R 20 is H or substituted or unsubstituted C 1-6 alkyl;
R 21 is H or substituted or unsubstituted C 1-6 alkyl;
R 22 is H or substituted or unsubstituted C 1-6 alkyl;
R 23 is H or substituted or unsubstituted C 1-6 alkyl;
R 24 is H or substituted or unsubstituted C 1-6 alkyl;

and including compounds:
N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2-sulfonamide;
N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; and
N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide;

and with the provisos that:
a) R 6 is not the same as R 5 ;
b) when R 5 is a substituted heterocycle then it is not

c) when R 6 is 2-thienyl then R 7 , R 8 , R 16 and R 18 are not all hydrogen in same time; and
d) the compound is not of the following structures:

2. The method of claim 1 , wherein the compound administered is a compound of Formula I, or an enantiomer, a diastereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein:
R 6 is 2-benzofuran or 2-thienyl.

3. The method of claim 1 , wherein the compound administered is a compound of Formula I, or an enantiomer, a diastereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein:
R 6 is 2-benzofuran.

4. The method of claim 1 , wherein the compound administered is a compound of Formula I, or an enantiomer, a diastereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein:
R 6 is 2-thienyl.

5. The method of claim 1 , wherein the compound administered is a compound of Formula I, or an enantiomer, a diastereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein:
R 1 is H or substituted or unsubstituted C 1-6 alkyl;
R 2 is H or substituted or unsubstituted C 1-6 alkyl;
R 5 is substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C 3-8 cycloalkyl, substituted or unsubstituted C 3-8 cycloalkenyl or is substituted or unsubstituted C 6-10 aryl;
R 6 is 2-benzofuran, 2-thienyl, 5-chloro-2-thienyl, 4,5-dichloro-2-thienyl, 4-chloro-3-methylphenyl, or 4-chloro-3-trifluoromethylphenyl;
R 7 is H, substituted or unsubstituted C 1-6 alkyl;
R 8 is H, substituted or unsubstituted C 1-6 alkyl;
R 16 is H; and
R 18 is H.

6. The method of claim 1 , wherein the compound administered is a compound of Formula I, or an enantiomer, a diastereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein:
R 1 is H;
R 2 is H;
R 5 is 2 thienyl, phenyl, phenyl-4-acetamide, 4-chloro-3-trifluoromethylphenyl, -1-methyl-1H-imidazole, 3-pyridine, 2 aminophenyl, 1,3-dimethyl-1H-pyrazole, 1-methyl-1H-pyrazole, 1-methyl-1H-imidazole, 4-(1H-pyrazol-1-yl)phenyl, 1,3-thiazol-4-yl)phenyl, 4-(1,3-oxazol-5-yl)phenyl, 2-(methylamino)benzoate, 1-methyl-1H-indole, 2-oxoindoline, 1-methyl-2,3-dioxoindoline, 1-methyl-2-oxoindoline, 2-furan, 4-biphenyl, 3,5-difluorophenyl, 3,5-dichlorophenyl, -3,5-dimethylisoxazole, 4-chloro-2,5-difluorophenyl, 4-(2-methylphenoxy)phenyl, 5-isoxazol-3-ylthiophene, 2,6-dichlorophenyl, 4-(methylsulfonyl)phenyl, 3,4-difluorophenyl, 4-chloro-3-methylphenyl, 2-oxo-2,3-dihydro-1,3-benzoxazole, 4-benzoic acid, 2-methoxybenzoic acid, 3-cyanophenyl, 4-tert-butylphenyl, 1,3-benzothiazole, 1H-1,2,4-triazole, 2-chloro-1,3-benzothiazole, 2,4-dimethoxyphenyl, 2,5-dichloro-3-thienyl, 3-methoxyphenyl, 3-(methylsulfonyl)phenyl, 3-chloro-2-methylphenyl, 4phenylpropanoic acid, 2-ethoxybenzoic acid, 2-methylphenyl}acetamide, 3,5-bis(trifluoromethyl)phenyl, 1H-pyrazole, 4-(trifluoromethoxy)phenyl, 4-(benzyloxy)phenyl, 2-chloro-4-fluorobenzoic acid, thiophene-2-carboxylate, 4-fluorobenzoic acid, 2-chloro-quinoline, 2,3-dihydro-1H-inden, 1-nathphtyl, 1,3-benzodioxole, 3,5-dichloro-2-hydroxyphenyl, 2-benzofuran, quinoline, 4-methylbenzoate, 2,4-dimethyl-1,3-thiazole, 4-methyl-1,3-thiazol-2-yl}acetamide, 5-chloro-8-quinoline, 2,4,5-trifluorophenyl, 3,4-dimethoxyphenyl, 3,5-dimethyl-1H-pyrazole, 1-(phenylsulfonyl)-1H-pyrrole, N-acetylindoline, 1,3,4-oxadiazol-2-yl-phenyl, 3-(1-methyl-1H-pyrazol-3-yl)phenyl, 2-thienylsulfonyl)amino]phenyl-4-methyl, 2-oxo-2H-chromene, 6-phenyl-3-pyridine, 2-chloro-4-(trifluoromethyl)phenyl, 6-phenoxypyridine, 5-phenylthiophene, 2,5-dimethyl-3-thienyl, 2-chlorophenyl-4-acetamide, (5-chloro-2,4-difluorophenyl, 4-(1-methyl-1H-pyrazol-3-yl)phenyl, 5-methyl-1-benzothiophene, 2,5-dimethylfuran, 4-(pyrrolidin-1-ylsulfonyl)phenyl, methyl-2-methyl-3-furoate, 3-oxo-3,4-dihydro-2H-1,4-benzoxazine, 2,4-dichloro-benzoic acid, 5-{[(dimethylamino) carbonyl]amino)-2-ethoxyphenyl, 2-methoxyphenyl}acetamide, 2-imidazo[2,1-b][1,3]thiazole, 6-morpholin-4-ylpyridine, 3-[(6-methylpyrazin-2-yl)oxy]phenyl, 5-pyridin-2-ylthiophene, 3-pyrimidin-2-ylphenyl, 4-dihydro-2H-pyrido[3,2-b][1,4]oxazine, 6-(dimethylamino)-2-naphthyl, 2-(methyl sulfonyl)phenyl, 3-methyl-8-quinoline, 5-isoxazol-5-ylthiophene, 5-(dimethylamino)-1-naphthyl, 2-chloro-thienyl, methyl, ethyl, benzyl, isso-butyl, 2,2-dimethylchromane, 2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine, 4-methyl-3,4-dihydro-2H-1,4-benzoxazine, 4-acetyl-3,4-dihydro-2H-1,4-benzoxazine, 4-(benzyloxy)phenyl, 2,4-dimethyl-1,3-thiazole, 3,5-dimethylisoxazole, 5-chloro-3-methyl-1-benzothien-2-yl, 2-chloro-4-fluorobenzoic acid, 4-methyl-1,3-thiazol-2-yl}acetamide, 1H-1,2,4-triazole, phenyl}propanoic acid, 5-chlorothiophene-2-carboxylate, 3-phenylacetamide, 2-oxoindoline, 2-oxo-2,3-dihydro-1,3-benzoxazole, 5-isoxazol-3-yl-2-thienyl, 2-chloroquinoline, 1-(phenylsulfonyl)-1H-pyrrole, 2,5-dichloro-3-thienyl, 5-{[(dimethyla

Assignees

• Allergan Inc

Inventors

• Yuan Haiqing
• Beard Richard L
• Garst Michael E
• Liu Xiaoxia
• Donello John E
• Viswanath Veena

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P27/00

  Drugs for disorders of the senses · CPC title

• A61P27/02

  Ophthalmic agents · CPC title