Arylsulfonamide derivatives for use as ccr3 antagonists in the treatment of inflammatory and immunological disorders

1. A sulfonamide derivative of the formula (I), its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof:

X represents phenyl, which is substituted by 0 to 5 substituents independently selected from the group consisting of R 1 , R 2 , R 3 , R 4 and R 0 , or pyridine, which is substituted by 0 to 5 substituents independently selected from the group consisting of R 1 , R 2 , R 3 and R 4

wherein

R 1 is hydrogen, halogen, hydroxy, straight- or branched-C 1-6 alkyl optionally mono-, di-, or tri-substituted by halogen, or by straight- or branched-C 1-6 alkoxy, straight- or branched-C 1-6 alkoxy carbonyl, amino, straight- or branched-C 1-6 alkylamino, di(straight- or branched-C 1-6 alkyl)amino, straight- or branched-C 1-6 alkanoyl, nitro, or phenyl,

R 2 is hydrogen, halogen, straight- or branched-C 1-6 alkyl optionally mono-, di-, or tri- substituted by halogen, or by straight- or branched-C 1-6 alkoxy, or cyano, or

R 1 and R 2 together form benzene ring or C 5-8 cycloalkyl fused to the adjacent phenyl,

R 3 is hydrogen, halogen, or straight- or branched-C 1-6 alkyl,

R 4 is hydrogen, halogen, or straight- or branched-C 1-6 alkyl,

R 0 is hydrogen, halogen, or straight- or branched-C 1-6 alkyl,

Y represents O, NH, NCH 3 S, S(O), or SO 2 ;

Z 1 represents CH;

Z 2 represents CH;

R 5 is chloro, iodo, nitro, or cyano;

R 6 is hydrogen;

R 7 represents

wherein

n represents an integer selected from 1 to 3,

m represents an integer selected from 0 to 3,

R 71 is hydrogen, C 3-8 cycloalkyl optionally interrupted by NH, N—CH 3 or O, straight- or branched C 1-6 alkoxycarbonyl, phenyl optionally substituted by straight- or branched C 1-6 alkyl, benzyl, formyl, or

straight- or branched C 1-6 alkyl

wherein the alkyl is optionally substituted by hydroxy, straight- or branched-C 1-6 alkoxy, hydroxy straight- or branched-C 1-6 alkoxy, carboxy, straight- or branched-C 1-6 alkoxycarbonyl, straight- or branched-C 1-6 alkylthio, di(straight- or branched-C 1-6 alkyl)amino, from 1 to 3 halogens, or C 3-8 cycloalkyl optionally interrupted by NH or O,

R 711 and R 712 are independently selected from the group consisting of hydrogen, halogen, hydroxy, carboxy, cyano, straight- or branched-C 1-6 alkyl optionally substituted by hydroxy, carboxy, from 1 to 3 halogens, carbamoyl, di(straight-or branched C 1-6 alkyl)amino carbonyl, and —NR 711a R 711b ,

wherein

R 711a and R 711b are independently selected from the group consisting of hydrogen, straight- or branched-C 1-6 alkyl, straight- or branched-C 1-6 alkanoyl, and straight- or branched-C 1-6 alkylsulfonyl, or

R 71 and R 711 may form, together with the N atom adjacent to R 71 , a 5 to 8 membered saturated ring.

2. The sulfonamide derivative of the formula (I), its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof as claimed in claim 1 ,

wherein

R 1 is halogen, or straight- or branched-C 1-6 alkyl optionally mono-, di-, or tri-substituted by halogen;

R 2 is halogen, or straight- or branched-C 1-6 alkyl optionally mono-, di-, or tri-substituted by halogen;

R 3 is hydrogen;

R 4 is hydrogen;

R 0 is hydrogen;

Y is O, NH, NCH 3 , S, S(O), or SO 2 ;

R 5 is halogen, nitro, or cyano;

R 6 hydrogen; and

R 7 represents

wherein

n represents an integer selected from 1 to 3,

m represents an integer selected from 0 to 3,

R 71 is hydrogen, straight- or branched-C 1-6 alkyl optionally substituted by hydroxy or hydroxy straight- or branched-C 1-6 alkoxy, C 3-8 cycloalkyl, straight- or branched-C 1-6 alkoxycarbonyl, phenyl optionally substituted by straight- or branched-C 1-6 alkyl, benzyl, or formyl,

R 711 and R 712 are independently selected from the group consisting of hydrogen, halogen, carboxy, and straight- or branched C 1-6 alkyl, or

R 71 and R 711 may form, together with the N atom adjacent to R 71 , a 5 to 8 membered saturated ring.

3. The sulfonamide derivative of the formula (I), its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof as claimed in claim 1 ,

wherein

R 1 and R 2 are identical or different and represent chloro, or methyl;

R 3 is hydrogen or fluoro;

R 4 is hydrogen;

R 0 is hydrogen;

Y is O, NH, NCH 3 , S, S(O), or SO 2 ;

R 5 is chloro, iodo, nitro, or cyano;

R 6 is hydrogen; and

R 7 represents

wherein

n represents an integer selected from 1 to 3,

m represents an integer selected from 0 to 3,

R 71 is hydrogen, straight- or branched-C 1-6 alkyl optionally substituted by hydroxy or hydroxy straight- or branched-C 1-6 alkoxy, C 3-8 cycloalkyl, straight- or branched-C 1-6 alkoxycarbonyl, phenyl optionally substituted by straight- or branched-C 1-6 alkyl, benzyl, or formyl,

R 711 and R 712 are independently selected from the group consisting of hydrogen, halogen, carboxy, and straight-or branched-C 1-6 alkyl, or

R 71 and R 711 may form, together with the N atom adjacent to R 71 , a 5 to 8 membered saturated ring.

4. The sulfonamide derivative of the formula (I), its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof as claimed in claim 1 ,

wherein

R 1 is hydrogen, fluoro, chloro, bromo, methyl, isopropyl, butyl, tert-butyl, trifluoromethyl, methoxy, amino, dimethylamino, acetyl, or nitro;

R 2 is hydrogen, fluoro, chloro, methyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, or cyano;

R 3 is hydrogen or fluoro;

R 4 is hydrogen;

R 0 is hydrogen;

Y is O, NH, NCH 3 , S, S(O), or SO 2 ;

R 5 is chloro, iodo, nitro, or cyano;

R 6 is hydrogen; and

R 7 represents

wherein

n represents an integer 1,

m represents an integer selected from 1 or 2,

R 71 represents hydrogen, methyl, ethyl or isopropyl;

R 711 represents hydrogen, methyl, or carboxy;

R 712 represents hydrogen or methyl, or

R 71 and R 711 may form, together with the N atom adjacent to R 71 , a 5 membered saturated ring.

5. The sulfonamide derivative of the formula (I-2), its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof;

wherein

R 1 is hydrogen, halogen, straight- or branched-C 1-6 alkyl optionally mono-, di-, or tri-substituted by halogen, straight- or branched-C 1-6 alkoxy, straight- or branched-C 1-6 alkoxy carbonyl, amino, straight- or branched -C 1-6 alkylamino, di(straight- or branched-C 1-6 alkyl)amino, straight- or branched-C 1-6 alkanoyl, or nitro,

R 2 is hydrogen, halogen, straight- or branched-C 1-6 alkyl optionally mono-, di-, or tri-substituted by halogen, straight- or branched-C 1-6 alkoxy, or cyano, or

R 1 and R 2 may form benzene ring or C 5-8 cycloalkyl fused to the adjacent phenyl;

R 3 is hydrogen or halogen,

Y represents O, NH, NCH 3 , S, S(O), or SO 2 ;

R 5 is chloro, iodo, nitro, or cyano;

R 6 is hydrogen;

R 7 represents

wherein

n represents an integer selected from 1 to 3,

m represents an integer selected from 0 to 3,

R 71 is hydrogen, straight- or branched-C 1-6 alkyl optionally substituted by hydroxy or hydroxy straight- or branched-C 1-6 alkoxy, C 3-8 cycloalkyl, straight- or branched-C 1-6 alkoxycarbonyl, phenyl optionally substituted by straight- or branched-C 1-6 alkyl, benzyl, or formyl,

R 711 and R 712 are independently selected from the group consisting of hydrogen, halogen, hydroxy, carboxy, cyano, straight- or branched C 1-6 alkyl optionally substituted by hydroxy, carboxy, or 1 to 3 halogens, carbamoyl, di (straight- or branched C 1-6 alkyl) amino carbonyl, or —NR 711a R 711b

wherein

R 711a and R 711b are independently selected from the group consisting of hydrogen, straight- or branched-C 1-6 alkyl, straight- or branched-C 1-6 alkanoyl, or straight- or branched-C 1-6 alkylsulfonyl, or

R 71 and R 711 may form, together with the N atom adjacent to R 71 , a 5 to 8 membered saturated ring.

6. The sulfonamide derivative of the formula (I-2), its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof as claimed in claim 5 ,

wherein

R 1 is hydrogen, halogen, or straight- or branched-C 1-6 alkyl optionally mono-, di-, or tri-substituted by halogen;

R 2 is hydrogen, halogen, or straight- or branched-C 1-6 alkyl optionally mono-, di-, or tri-substituted by halogen;

R 3 is hydrogen or halogen,

Y is O, NH, NCH 3 , S, S(O), or SO 2 ;

R 5 is halogen, nitro, or cyano;

R 6 is hydrogen; and

R 7 represents

wherein

n represents an integer selected from 1 to 3,

m represents an integer selected from 0 to 3,

R 71 is hydrogen, straight- or branched-C 1-6 alkyl optionally substituted by hydroxy or hydroxy straight- or branched-C 1-6 alkoxy, C 3-8 cycloalkyl, straight- or branched-C 1-6 alkoxycarbonyl, phenyl optionally substituted by straight- or branched-C 1-6 alkyl, benzyl, or formyl,

R 711 represents hydrogen, methyl, or carboxy,

R 712 represents hydrogen or methyl, or

R 71 and R 711 may form, together with the N atom adjacent to R 71 , a 5 to 8 membered saturated ring.

7. The sulfonamide derivative of the formula (I-2), its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof as claimed in claim 5 ,

wherein

R 1 , R 2 and R 3 are independently selected from the group consisting of hydrogen, chloro, and methyl;

Y is O, NH, NCH 3 , S, S(O), or SO 2 ;

R 5 is chloro, iodo, nitro, or cyano;

R 6 is hydrogen; and

R 7 represents

wherein

n represents an integer selected from 1 to 3,

m represents an integer selected from 1 to 3,

R 71 is hydrogen, straight- or branched-C 1-6 alkyl optionally substituted by hydroxy or hydroxy straight- or branched-C 1-6 alkoxy, C 3-8 cycloalkyl, straight- or branched-C 1-6 alkoxycarbonyl, phenyl optionally substituted by straight- or branched-C 1-6 alkyl, benzyl, or formyl,

R 711 represents hydrogen, methyl, or carboxy or

R 71 and R 711 may form, together with the N atom adjacent to R 71 , a 5 to 8 membered saturated ring.

R 1 is hydrogen, fluoro, chloro, bromo, methyl, isopropyl, butyl, tert-butyl, trifluoromethyl, methoxy, amino, dimethylamino, acetyl, or nitro;

R 2 is hydrogen, fluoro, chloro, methyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, or cyano;

R 3 is hydrogen or fluoro;

Y is O, NH, NCH 3 , S, S(O), or SO 2 ;

R 5 is hydrogen, fluoro, chloro, bromo, iodo, trifluoromethyl, hydroxy, methoxy, amino, acetylamino, isobutylcarbonylamino, tert-butylcarbonylamino, benzoylamino, benzylcarbonylamino, phenethylcarbonylamino, methylbenzoylamino, naphthylcarbonylamino, thenoylamino, nitro, cyano, methylsulfonyl, dimethyaminosulfonyl, piperazinosulfonyl, dimethyaminocarbonyl, or piperazinocarbonyl;

R 6 is hydrogen, methyl, or methoxy; or

R 5 and R 6 may form a pyrrole ring fused to adjacent phenyl, and

R 7 represents

8. The sulfonamide derivative of formula (I-2), its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof as claimed in claim 5 ,

wherein

R 1 is chloro, bromo, or methyl;

R 2 is hydrogen, chloro, bromo, or methyl;

R 3 is hydrogen or fluoro;

Y represents O, S, or S(O);

R 5 represents hydrogen, chloro, nitro, or cyano;

R 6 represents hydrogen;

R 7 represents

wherein

R 71 represents hydrogen, methyl, ethyl or isopropyl;

R 711 represents hydrogen, methyl or carboxy; and

R 712 represents hydrogen or methyl.

9. The sulfonamide derivative, its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof as claimed in claim 1 , wherein said sulfonamide derivative is selected from the group consisting of:

1-{[2-(3,5-dimethylphenoxy)-5-nitrophenyl]sulfonyl}-4-ethylpiperazine,

1-{[2-(3,5-dichlorophenoxy)-5-nitrophenyl]sulfonyl}piperazine,

1-{[2-( 3,5-dimethylphenoxy)-5-nitrophenyl]sulfonyl}-4-isopropylpiperazine,

4-(3,5-dimethylphenoxy)-3-(1-piperazinylsulfonyl)benzonitrile,

1-{[5-chloro-2-(3,5-dimethylphenoxy)phenyl]sulfonyl}-4-ethylpiperazine,

1-{[2-(3,5-dichlorophenoxy)-5-nitrophenyl]sulfonyl}-4-( 1-pyrrolidinyl)piperidine,

4-(3,5-dichlorophenoxy)-3-(1-piperazinylsulfonyl)benzonitrile,

4-[(3,5-dichlorophenyl)sulfanyl]-3-(1-piperazinylsulfonyl)benzonitrile,

4-[(3,5-dichlorophenyl)sulfinyl]-3-(1-piperazinylsulfonyl)benzonitrile,

1-{[2-(3,5-dibromophenoxy)-5-nitrophenyl]sulfonyl}piperazine,

1-{[2-(3,5-dichloro-2-fluorophenoxy)-5-nitrophenyl]sulfonyl}piperazine,

1-{[5-cyano-2-(3,5-dichlorophenoxy)phenyl]sulfonyl}-2-piperazinecarboxylic acid,

1-{[2-(3,5-dichlorophenoxy)-5-nitrophenyl]sulfonyl}-2-piperazinecarboxylic acid,

1-{[2-(3,5-dimethylphenoxy)-5-nitrophenyl]sulfonyl}-1,4-diazepane,

1-{[2-(3,5-dichlorophenoxy)-5-nitrophenyl]sulfonyl}-1,4-diazepane,

1-{[2-(3,5-dichlorophenoxy)-5-nitrophenyl]sulfonyl}-3,5-dimethylpiperazine,

3-(1,4-diazepan-1-ylsulfonyl)-4-(3,5-dichlorophenoxy)benzonitrile, and

3-(1,4-diazepan-1-ylsulfonyl)-4-[(3,5-dichlorophenyl)sulfanyl]benzonitrile.

10. A compound of formula (I-2), its tautomeric or stereoisomeric form, or a salt thereof as claimed in claim 5 ,

wherein

R 1 is hydrogen, fluoro, chloro, bromo, methyl, isopropyl, butyl, tert-butyl, trifluoromethyl, methoxy, amino, dimethylamino, acetyl, or nitro;

R 2 is hydrogen, fluoro, chloro, methyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, or cyano; or

R 3 is hydrogen or flouro;

Y is O, NH, NCH 3 , S, S(O), or SO 2 ;

R 5 is hydrogen, fluoro, chloro, bromo, iodo, trifluoromethyl, hydroxy, methoxy, amino, acetylamino, isobutylcarbonylamino, tert-butylcarbonylamino, benzoylamino, benzylcarbonylamino, phenethylcarbonylamino, methylbenzoylamino, napthylcarbonylamino, thenoylamino, nitro, cyano, methylsulfonyl, dimethylaminosulfonyl, piperazinosulfonyl, dimethylaminocarbonyl, or piperinocarbonyl;

R 6 is hydrogen, methyl, or methoxy; or

R 5 and R 6 may form a pyrrole ring fused to adjacent phenyl; and

R 7 represents

wherein

n represents an integer 1;

m represents an integer 1 or 2;

R 71 is hydrogen, methyl, ethyl, isopropyl, sec-butyl, branched pentyl, hydroxyethyl, hydroxyethoxyethyl, cyclopentyl, cyclohexyl, tert-butoxyethyl, phenyl, tolyl, benzyl, or formyl;

R 711 is hydrogen methyl, or carboxy;

R 712 is hydrogen or methyl; or

R 71 and R 711 may form, together with the N atom adjacent to -R 71 , a 5 membered saturated ring.

11. A compound of claim 1 , its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof, wherein the compound is selected from the group consisting of:

1-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-difluorophenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-dimethoxyphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-bis(trifluoromethyl)phenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-di-tert-butylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3-isopropyl-5-methylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3-isopropyl-5-methylphenoxy)-5-nitrophenylsulfonyl)piperazine,

3-(4-nitro-2-(piperazin-1-ylsulfonyl)phenoxy)benzonitrile,

1-(2-(naphthalen-1-yloxy)-5-nitrophenylsulfonyl)piperazine,

1-(5-nitro-2-(o-tolyloxy)phenylsulfonyl)piperazine,

4-(4-nitro-2-(piperazin-1-ylsulfonyl)phenoxy)aniline,

1-(2-(2-fluorophenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3-fluorophenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(5-nitro-2-(p-tolyloxy)phenylsulfonyl)piperazine,

1-(5-nitro-2-(m-tolyloxy)phenylsulfonyl)piperazine,

1-(5-nitro-2-phenoxyphenylsulfonyl)piperazine,

1-(2-(4-methoxyphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(4-fluorophenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(4-tert-butylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(4-chlorophenoxy)-5-nitrophenylsulfonyl)piperazine,

4-(4-nitro-2-(piperazin-1-ylsulfonyl)phenoxy)benzonitrile,

1-(5-nitro-2-(m-tolyloxy)phenylsulfonyl)piperazine,

1-(2-(3-fluorophenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(2-methoxyphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(2-chlorophenoxy)-5-nitrophenylsulfonyl)piperazine,

2-(4-nitro-2-(piperazin-1-ylsulfonyl)phenoxy)benzonitrile,

1-(2-(4-nitro-2-(piperazin-1-ylsulfonyl)phenoxy)phenyl)ethanone,

1-(3-(4-nitro-2-(piperazin-1-ylsulfonyl)phenoxy)phenyl)ethanone,

N,N-dimethyl-3-(4-nitro-2-(piperazin-1-ylsulfonyl)phenoxy)aniline,

1-(2-(3,5-dichlorophenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(5-nitro-2-(3-(trifluoromethyl)phenoxy)phenylsulfonyl)piperazine,

1-(2-(3-tert-butylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3-methoxy-5-methylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(5-nitro-2-(3-nitrophenoxy)phenylsulfonyl)piperazine,

1-(2-(3-bromophenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(2-butylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-dichlorophenoxy)-5-fluorophenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)-4-methylphenylsulfonyl)piperazine,

methyl 5-(4-nitro-2-(piperazin-1-ylsulfonyl)phenoxy)nicotinate,

1-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)-2,5-dimethylpiperazine,

1-(2-(5-chloropyridin-3-yloxy)-5-nitrophenylsulfonyl)piperazine,

1-(5-chloro-2-(3,5-dichlorophenoxy)phenylsulfonyl)piperazine,

1-(5-bromo-2-(3,5-dichlorophenoxy)phenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)-6-fluorophenylsulfonyl)piperazine,

1-(2-(4-chloro-3-methylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(5-nitro-2-(2,3,6-trimethylphenoxy)phenylsulfonyl)piperazine,

1-(2-(2,3-dimethylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,4-dimethylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(2,5-dimethylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(5-nitro-2-(2,3,5-trimethylphenoxy)phenylsulfonyl)piperazine,

1-(2-(2-isopropyl-5-methylphenoxy)-5-nitrophenylsulfonyl)piperazine,

3-(4-nitro-2-(piperazin-1-ylsulfonyl)phenoxy)aniline,

1-(2-(biphenyl-3-yloxy)-5-nitrophenylsulfonyl)piperazine,

1-(5-nitro-2-(3,4,5-trimethylphenoxy)phenylsulfonyl)piperazine,

1-(2-(6-methylpyridin-3-yloxy)-5-nitrophenylsulfonyl)piperazine,

3-methyl-5-(4-nitro-2-(piperazin-1-ylsulfonyl)phenoxy)phenol hydrochloride,

1-(5-nitro-2-(5,6,7,8-tetrahydronaphthalen-2-yloxy)phenylsulfonyl)piperazine,

1-(5-nitro-2-(2,3,4,5,6-pentafluorophenoxy)phenylsulfonyl)piperazine,

1-(5-nitro-2-(2,3,5,6-tetrafluorophenoxy)phenylsulfonyl)piperazine,

1-(2-(5-methyl-2-nitrophenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(4-chloro-3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(2-chloro-5-methylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(4-chloro-2-isopropyl-5-methylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(2,3-dichlorophenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(2,5-dichlorophenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3-chloro-4-fluorophenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(5-nitro-2-(2,3,5-trichlorophenoxy)phenylsulfonyl)piperazine,

2-(4-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)piperazin-1-yl)ethanol,

2-(2-(4-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)piperazin-1-yl)ethoxy)ethanol,

1-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)-3,5-dimethylpiperazine,

1-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)-2,6-dimethylpiperazine,

1-(2-(3,5-dimethylphenylthio)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-dichlorophenylthio)-5-nitrophenylsulfonyl)-4-((tetrahydrofuran-2-yl)methyl)piperazine,

ethyl 3-(4-(2-(3,5-dichlorophenylthio)-5-nitrophenylsulfonyl)piperazin-1-yl)propanoate,

1-(2-(3,5-dichlorophenylthio)-5-nitrophenylsulfonyl)-4-(3-methoxypropyl)piperazine,

3-(4-(2-(3,5-dichlorophenylthio)-5-nitrophenylsulfonyl)piperazin-1-yl)propanoic acid,

1-(5-nitro-2-(phenylthio)phenylsulfonyl)piperazine,

1-(2-(2,4,6-trimethylphenylthio)-5-nitrophenylsulfonyl)piperazine,

1-(5-nitro-2-(3-methylphenylthio)phenylsulfonyl)piperazine,

1-(2-(3-chlorophenylthio)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-dichlorophenylthio)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3-fluorophenylthio)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-bis(trifluoromethyl)phenylthio)-5-nitrophenylsulfonyl)piperazine,

1-(2-(naphthalen-2-ylthio)-5-nitrophenylsulfonyl)piperazine,

N-(3,5-dimethylphenyl)-4-nitro-2-(piperazin-1-ylsulfonyl)aniline,

N-(3,5-dichlorophenyl)-4-nitro-2-(piperazin-1-ylsulfonyl)aniline,

4-nitro-2-(piperazin-1-ylsulfonyl)-N-2-methylphenylaniline,

4-nitro-2-(piperazin-1-ylsulfonyl)-N-3-methylphenylaniline,

4-nitro-2-(piperazin-1-ylsulfonyl)-N-4-methylphenylaniline,

N-(2-chlorophenyl)-4-nitro-2-(piperazin-1-ylsulfonyl)aniline,

N-(3-chlorophenyl)-4-nitro-2-(piperazin-1-ylsulfonyl)aniline,

N-(4-chlorophenyl)-4-nitro-2-(piperazin-1-ylsulfonyl)aniline,

N-(2-fluorophenyl)-4-nitro-2-(piperazin-1-ylsulfonyl)aniline,

N-(3-fluorophenyl)-4-nitro-2-(piperazin-1-ylsulfonyl)aniline,

N-(4-fluorophenyl)-4-nitro-2-(piperazin-1-ylsulfonyl)aniline,

N-(2-methoxyphenyl)-4-nitro-2-(piperazin-1-ylsulfonyl)aniline,

1-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)-4-methylpiperazine,

1-cyclohexyl-4-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)-4-phenylpiperazine,

1-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)-4-(4-methylphenyl)piperazine,

1-benzyl-4-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)piperazine,

4-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)piperazine-1-carbaldehyde,

1-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)-4-isopropylpiperazine,

1-sec-butyl-4-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)-4-(pentan-2-yl)piperazine,

1-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)-4-(pentan-3-yl)piperazine,

1-cyclopentyl-4-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)-4-((tetrahydrofuran-2-yl)methyl)piperazine,

1-(2-(3,5-dichlorophenoxy)-5-nitrophenylsulfonyl)-4-((tetrahydrofuran-2-yl)methyl)piperazine,

1-(2-(3,5-dimethylphenylthio)-5-nitrophenylsulfonyl)-4-((tetrahydrofuran-2-yl)methyl)piperazine,

2-(4-(2-(3,5-dichlorophenoxy)-5-nitrophenylsulfonyl)piperazin-1-yl)-N,N-diethylethanamine,

2-(4-(2-(3,5-dichlorophenoxy)-5-nitrophenylsulfonyl)piperazin-1-yl)-N,N-dimethylethanamine,

1-(2-(3,5-dichlorophenoxy)-5-nitrophenylsulfonyl)-4-( 1-methylpiperidin-4-yl)piperazine,

1-(2-(3,5-dimethylphenoxy)-5-nitrophenylsulfonyl)-4-(3,3,3-trifluoropropyl)piperazine,

1-(2-(3,5-dichlorophenoxy)-5-nitrophenylsulfonyl)-4-(3,3,3-trifluoropropyl)piperazine,

1-(2-(3,5-dichlorophenoxy)-5-nitrophenylsulfonyl)-4-(3-methoxypropyl)piperazine,

ethyl 3-(4-(2-(3,5-dichlorophenoxy)-5-nitrophenylsulfonyl)piperazin-1-yl)propanoate,

1-(5-chloro-2-(3,5-dimethylphenoxy)phenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)-5-iodophenylsulfonyl)-4-ethylpiperazine,

1-(2-(3,5-dimethylphenoxy)-5-iodophenylsulfonyl)piperazine,

4-(3,5-dimethylphenoxy)-2-methyl-5-(piperazin-1-ylsulfonyl)aniline,

1-(2-(3,5-dimethylphenoxy)-5-fluorophenylsulfonyl)piperazine,

4-(3,5-dichlorophenoxy)-3-(4-(3-methoxypropyl)piperazin-1-ylsulfonyl)benzonitrile,

4-(3,5-dichlorophenylthio)-3-(piperazin-1-ylsulfonyl)benzonitrile,

4-(3,5-dichlorophenylthio)-3-(4-(3-(methylthio)propyl)piperazin-1-ylsulfonyl)benzonitrile,

3-(1,4-diazepan-1-ylsulfonyl)-4-(3,5-dichlorophenylthio)benzonitrile,

4-(3,5-dichlorophenylsulfonyl)-3-(piperazin-1-ylsulfonyl)benzonitrile,

4-(3,5-dichlorophenylamino)-3-(piperazin-1-ylsulfonyl)benzonitrile,

4-((3,5-dichlorophenyl)(methyl)amino)-3-(piperazin-1-ylsulfonyl)benzonitrile,

N-(3,5-dimethylphenyl)-N-methyl-4-nitro-2-(piperazin-1-ylsulfonyl)aniline, and

1-(2-(3,5-dimethylphenoxy)-4-nitrophenylsulfonyl)piperazine.

12. A compound of claim 11 , wherein the salt is a hydrochloride, dihydrochloride, trihydrochloride, or a mono-, di- or tri-trifluoroacetate.

13. A compound of claim 12 , wherein the salt is a hydrochloride.

14. A pharmaceutical composition comprising a compound of claim 1 and one or more pharmaceutically acceptable carriers or excipients.

15. The pharmaceutical composition of claim 14 , wherein the compound, its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof is in unit dosage form.

16. A method of treating a CCR3 related disease or disorder comprising administering a compound of claim 1 , wherein the disease or disorder is selected from the group consisting of arthritis, asthma, allergic rhinitis, atopic dermatitis, athero sclerosis, Grave's disease, HIV infection, lung granuloma, and Alzheimer's disease.

17. A compound, its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof, wherein the compound is selected from the group consisting of:

1-(2-(3,5-dimethylphenoxy)-5-(piperazin-1-ylsulfonyl)phenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)-5-(methylsulfonyl)phenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)phenylsulfonyl)piperazine,

(4(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)phenyl)(piperazin-1-yl)methanone,

1-(2-(3,5-dimethylphenoxy)-5-(trifluoromethyl)phenylsulfonyl)piperazine,

1-(2-(3,5-dichlorophenoxy)-4-methyl-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)-4-(trifluoromethyl)phenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)-4-methoxy-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)-4-methoxyphenylsulfonyl)piperazine hydrochloride,

1-(2-(3,5-dimethylphenoxy)-4-methoxy-5-nitrophenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)aniline,

1-(5-chloro-2-(3,5-dimethylphenoxy)-4-methylphenylsulfonyl)piperazine,

4-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)phenol,

1-(2-(3,5-dimethylphenoxy)-5-(methoxyphenylsulfonyl)piperazine,

1-(2-(3,5-dimethylphenoxy)-5-(fluorophenylsulfonyl)piperazine,

N-(4-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)phenyl)acetamide,

N-(4-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)phenyl)pivalamide,

N-(4-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)phenyl)3-methylbutanamide,

N-(4-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)phenyl)benzamide,

N-(4-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)phenyl)-4-methylbenzamide,

N-(4-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)phenyl)a-1-naphthamide,

N-(4-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)phenyl)-3-phenylpropanamide,

N-(4-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)phenyl)thiophene-2-carboxamide,

1-(5-bromo-2-(3,5-dimethylphenoxy)phenylsulfonyl)piperazine,

4-(3,5-dichlorophenoxy)-N,N-dimethyl-3-(piperazin-1-ylsulfonyl)benzamide,

4-(3,5-dimethylphenoxy)-N,N-dimethyl-3-(piperazin-1-ylsulfonyl)benzamide,

5-(3,5-dimethylphenoxy)-6-(piperazin-1-ylsulfonyl)-1H-indole,

2-chloro-4-(3,5-dimethylphenoxy)-5-(piperazin-1-ylsulfonyl)benzonitrile,

2-chloro-4-(3,5-dichlorophenoxy)-5-(piperazin-1-ylsulfonyl)benzonitrile,

4-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)benzoic acid,

3-(4-(tert-butoxycarbonyl)piperazin-1-ylsulfonyl)-4-(3,5-dichlorophenoxy)benzoic acid,

4-(3,5-dichlorophenoxy)-3-(piperazin-1-ylsulfonyl)benzoic acid,

4-(3,5-dichlorophenoxy)-3-(piperazin-1-ylsulfonyl)benzamide,

methyl 4-(3,5-dimethylphenoxy)-3-(piperazine-1-ylsulfonyl)benzoate,

2-chloro-4-(3,5-dimethylphenoxy)-5-(piperazin-1-ylsulfonyl)benzamide,

4-(3,5-dichlorophenoxy)-3-fluoro-5-(piperazin-1-ylsulfonyl)benzamide,

4-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)methanol,

N-(2-cyanoethyl)-4-(3,5-dimethylphenoxy)3-(piperazin-1-ylsulfonyl)benzamide,

N-(3-amino-3-oxopropyl)-4-(3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)benzamide,

3-(5-3,5-dimethylphenoxy)-3-(piperazin-1-ylsulfonyl)phenyl)-1H-tetrazol-1-yl)propanenitrile,

1-(2-(3,5-dimethylphenoxy)-5-(1H-tetrazol-5-yl)phenylsulfonyl)piperazine, and

1-(4-bromo-2-(3,5-dimethylphenoxy)phenylsulfonyl)piperazine.

18. A pharmaceutical composition comprising a compound of claim 17 and one or more pharmaceutically acceptable carriers or excipients.

19. A method of treating a CCR3 related disease or disorder comprising administering a compound of claim 17 , wherein the disease or disorder is selected from the group consisting of arthritis, asthma, allergic rhinitis, atopic dermatitis, athero sclerosis, Grave's disease, HIV infection, lung granuloma, and Alzheimer's disease.