Pyridylphenyl compounds for inflammation and immune-related uses

Abstract

The invention relates to compounds of structural formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein Y, L, X 1 , X 2 , Z, R 3 , R 4 , and n are defined herein. These compounds are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

1 . A compound represented by structural formula (II):  
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein:  
       Y 1  is a monocyclic optionally substituted aryl or a monocyclic optionally substituted heteroaryl, provided that Y 1  is not a substituted isoxazolyl or a substituted 1H-pyrrolyl;  
       L 1  is a linker selected from the group consisting of —NHCH 2 —, —CH 2 NH—, —NR—C(O)—, —OC(O)—, —C(O)O—, —C(S)—, —NR—C(S)—, or —C(S)—NR—;  
       one of X 1  or X 2  is CH or CZ and the other is N;  
       each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, —S(O) p -alkyl, —C(O)NRR, —(CH 2 ) k NRR, —(CH 2 ) k OR, —(CH 2 ) k SR, cyano, nitro, or lower haloalkoxy;  
       R, for each occurrence is independently selected from —H or an alkyl;  
       R 3  is H, an alkyl, a haloalkyl, a halo, a haloalkoxy, —OR 5 , —SR 5 , or —NR 6 R 7 ;  
       R 4  is a halo, a haloalkyl, cyano, nitro, —C(O)R 5 , —C(O)OR 5 , —C(O)SR 5 , —C(O)NR 9 R 10 , —C(S)R 5 , —C(S)OR 5 , —C(S)SR 5 , —C(S)NR 6 R 7 , —C(NR 8 )R 5 , —C(NR 8 )OR 5 , —C(NR 8 )SR 5 , —C(NR 8 )NR 6 R 7 , —S(O) p R 5 , —S(O) p NR 5 , —S(O) p OR 5 , P(O)(OR 5 ) 2 , —OP(O)(OR 5 ) 2 , —P(O)(R 5 ) 2 , an optionally substituted heterocyclyl, or an optionally substituted heteroaryl;  
       R 5 , for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;  
       R 6  and R 7 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 6  and R 7  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       R 8 , for each occurrence, is independently —H, a halo, an alkyl, —OR 5 , —NR 6 R 7 , —C(O)R 5 , —C(O)OR 5 , or —C(O)NR 6 R 7 ;  
       R 9  and R 10 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted 5- to 14-membered cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, or an optionally substituted heteroaryl selected from the group consisting of an optionally substituted pyridinyl, an optionally substituted thienyl, an optionally substituted pyrrolyl, an optionally substituted oxazolyl, an optionally substituted imidazolyl, an optionally substituted indolizinyl, an optionally substituted isoxazolyl, an optionally substituted pyrazolyl, an optionally substituted isothiazolyl, an optionally substituted pyridazinyl, an optionally substituted pyrimidinyl, an optionally substituted pyrazinyl, an optionally substituted triazinyl, an optionally substituted triazolyl, an optionally substituted pyridinyl, an optionally substituted thiadiazolyl, an optionally substituted pyrazinyl, an optionally substituted quinolinyl, an optionally substituted isoquniolinyl, an optionally substituted indazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzofuryl, an optionally substituted benzothiazolyl, an optionally substituted indolizinyl, an optionally substituted imidazopyridinyl, an optionally substituted tetrazolyl, an optionally substituted benzimidazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzothiazolyl, an optionally substituted benzothiadiazolyl, an optionally substituted benzoxadiazolyl, an optionally substituted indolyl, an optionally substituted tetrahydroindolyl, an optionally substituted azaindolyl, an optionally substituted imidazopyridyl, an optionally substituted qunizaolinyl, an optionally substituted purinyl, an optionally substituted pyrrolo[2,3]pyrimidyl, an optionally substituted pyrazolo[3,4]pyrimidyl or an optionally substituted benzo(b)thienyl; or R 9  and R 10  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       q, for each occurrence, is independently, an integer from 1 to 3;  
       k is for each occurrence, is independently, an integer from 1 to 4;  
       n is zero, 1 or 2; and  
       p, for each occurrence, is independently 1 or 2.  
     
   
   
       2 . The compound of  claim 1 , wherein Y 1  is an optionally substituted phenyl, an optionally substituted pyridinyl, an optionally substituted pyridazinyl, an optionally substituted isothiazolyl, an optionally substituted thiazolyl, an optionally substituted triazolyl, an optionally substituted oxadiazolyl, an optionally substituted oxazolyl, an optionally substituted thiadiazolyl, or an optionally substituted thiophenyl.  
   
   
       3 . The compound of  claim 2 , wherein Y 1  is an optionally substituted phenyl or an optionally substituted thiadiazolyl.  
   
   
       4 . The compound of  claim 3 , wherein Y 1  is an optionally substituted phenyl.  
   
   
       5 . The compound of  claim 4 , wherein Y 1  is substituted with one to two substituents.  
   
   
       6 . The compound of  claim 5 , wherein the one to two substituents are each independently a lower alkyl or a halo.  
   
   
       7 . The compound of  claim 6 , wherein Y 1  is a difluorophenyl.  
   
   
       8 . The compound of  claim 3 , wherein Y 1  is 4-methyl-1,2,3-thiadiazol-5-yl.  
   
   
       9 . The compound of  claim 1 , wherein L 1  is —NR—C(O)—.  
   
   
       10 . The compound of  claim 1 , wherein R is —H.  
   
   
       11 . The compound of  claim 1 , wherein R 4  is —C(O)OR 5 , a haloalkyl, an optionally substituted oxazolyl, an optionally substituted thiazolyl, an optionally substituted imidazolyl, an optionally substituted pyridinyl, an optionally substituted pyrazolyl, an optionally substituted pyrrolyl, an optionally substituted thiophenyl, an optionally substituted furanyl, an optionally substituted thiadiazolyl, an optionally substituted oxadiazolyl, or an optionally substituted tetrazolyl.  
   
   
       12 . The compound of  claim 11 , wherein R 4  is oxazol-2-yl, oxazol-5-yl, thiazol-2-yl, thiazol-5-yl, [1,3,4]oxadiazol-2-yl, trifluoromethyl, pyridin-3-yl, pyridin-2-yl, —C(O)OCH 2 CH 2 CH 3 , —C(O)OCH 2 CH 3 , or —C(O)OCH 3 .  
   
   
       13 . The compound of  claim 1 , wherein R 3  is —H, chloro, fluoro, bromo, methyl, or methoxy.  
   
   
       14 . The compound of  claim 1 , wherein n is 0.  
   
   
       15 . The compound of  claim 1 , wherein n is 1 and Z is methyl.  
   
   
       16 . The compound of  claim 1 , wherein X 1  is N.  
   
   
       17 . The compound of  claim 16 , wherein X 2  is CH.  
   
   
       18 . The compound of  claim 1 , wherein X 2  is N.  
   
   
       19 . The compound of  claim 18 , wherein X 1  is CH.  
   
   
       20 . The compound of  claim 1 , wherein: 
 Y 1  is an optionally substituted phenyl, an optionally substituted pyridinyl, an optionally substituted pyridazinyl, an optionally substituted isothiazolyl, an optionally substituted thiazolyl, an optionally substituted triazolyl, an optionally substituted oxadiazolyl, an optionally substituted oxazolyl, an optionally substituted thiadiazolyl, or an optionally substituted thiophenyl;    R 4  is —C(O)OR 5 , a haloalkyl, an optionally substituted oxazolyl, an optionally substituted thiazolyl, an optionally substituted imidazolyl, an optionally substituted pyridinyl, an optionally substituted pyrazolyl, an optionally substituted pyrrolyl, an optionally substituted thiophenyl, an optionally substituted furanyl, an optionally substituted thiadiazolyl, an optionally substituted oxadiazolyl, or an optionally substituted tetrazolyl;    one of X 1  or X 2  is CH; and    n is 0.    
   
   
       21 . The compound of  claim 20 , wherein L 1  is —NH—C(O)—.  
   
   
       22 . The compound of  claim 21 , wherein R 3  is —H, chloro, fluoro, bromo, methyl, or methoxy.  
   
   
       23 . The compound of  claim 22 , wherein, R 4  is oxazol-2-yl, oxazol-5-yl, thiazol-2-yl, thiazol-5-yl, [1,3,4]oxadiazol-2-yl, trifluoromethyl, pyridin-3-yl, pyridin-2-yl, —C(O)OCH 2 CH 2 CH 3 , —C(O)OCH 2 CH 3 , or —C(O)OCH 3 .  
   
   
       24 . The compound of  claim 23 , wherein Y 1  is a difluorophenyl.  
   
   
       25 . The compound of  claim 23 , wherein Y 1  is 4-methyl-1,2,3-thiadiazol-5-yl.  
   
   
       26 . The compound of  claim 1 , wherein the compound is selected from the group consisting of: 
 N-[6-(2-chloro-5-trifluoromethyl-phenyl)-pyridin-3-yl]-2,6-difluoro-benzamide;    N-[5-(2-Chloro-5-trifluoromethyl-phenyl)-pyridin-2-yl]-2,6-difluoro-benzamide;    N-[5-(2-Chloro-5-trifluoromethyl-phenyl)-pyridin-2-yl]-3-methyl-isonicotinamide;    N-[5-(2-Chloro-5-trifluoromethyl-phenyl)-pyridin-2-yl]-3-fluoro-isonicotinamide;    2,6-Difluoro-N-[5-(2-methyl-5-oxazol-2-yl-phenyl)-pyridin-2-yl]-benzamide;    4-Chloro-3-[6-(2,6-difluoro-benzoylamino)-pyridin-3-yl]-benzoic acid methyl ester;    3-[6-(2,6-Difluoro-benzoylamino)-pyridin-3-yl]-4-methyl-benzoic acid methyl ester;    N-[5-(2-Chloro-5-oxazol-2-yl-phenyl)-pyridin-2-yl]-2,6-difluoro-benzamide;    N-[5-(2-Chloro-5-trifluoromethyl-phenyl)-6-methyl-pyridin-2-yl]-2,6-difluoro-benzamide;    N-[5-(2-Chloro-5-thiazol-2-yl-phenyl)-pyridin-2-yl]-2,6-difluoro-benzamide;    N-[5-(2-Chloro-5-trifluoromethyl-phenyl)-4-methyl-pyridin-2-yl]-2,6-difluoro-benzamide;    3-[5-(2,6-Difluoro-benzoylamino)-pyridin-2-yl]-4-methyl-benzoic acid methyl ester;    2,6-Difluoro-N-[6-(2-methyl-5-oxazol-2-yl-phenyl)-pyridin-3-yl]-benzamide;    2,6-Difluoro-N-[4-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-benzamide;    2,6-Difluoro-N-[6-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-benzamide;    4-Methyl-[1,2,3]thiadiazole-5-carboxylic acid [5-(2-chloro-5-trifluoromethyl-phenyl)-pyridin-2-yl]-amide;    4-Methyl-[1,2,3]thiadiazole-5-carboxylic acid [5-(2-chloro-5-thiazol-2-yl-phenyl)-pyridin-2-yl]-amide;    4-Methyl-[1,2,3]thiadiazole-5-carboxylic acid [5-(2-methyl-5-oxazol-2-yl-phenyl)-pyridin-2-yl]-amide;    4-Methyl-[1,2,3]thiadiazole-5-carboxylic acid [5-(2-chloro-5-oxazol-2-yl-phenyl)-pyridin-2-yl]-amide;    2,6-Difluoro-N-[6-(2-methyl-5-oxazol-2-yl-phenyl)-pyridin-3-yl]-benzamide hydrochloride;    4-methyl-N-(5-(2-methyl-5-(oxazol-5-yl)phenyl)pyridin-2-yl)-1,2,3-thiadiazole-5-carboxamide;    3-(6-Benzoylamino-pyridin-3-yl)-4-chloro-benzoic acid methyl ester;    4-Chloro-3-[6-(2-methyl-benzoylamino)-pyridin-3-yl]-benzoic acid methyl ester;    4-Chloro-3-{6-[(3-methyl-pyridine-4-carbonyl)-amino]-pyridin-3-yl}-benzoic acid methyl ester;    4-Chloro-3-{6-[(3-fluoro-pyridine-4-carbonyl)-amino]-pyridin-3-yl}-benzoic acid methyl ester;    4-Chloro-3-{6-[(3-chloro-pyridine-4-carbonyl)-amino]-pyridin-3-yl}-benzoic acid methyl ester;    4-Chloro-3-{6-[(4-methyl-[1,2,3]thiadiazole-5-carbonyl)-amino]-pyridin-3-yl}-benzoic acid methyl ester;    4-Chloro-3-{6-[(4-methyl-[1,2,3]oxadiazole-5-carbonyl)-amino]-pyridin-3-yl}-benzoic acid methyl ester;    4-Chloro-3-{6-[(5-methyl-3H-[1,2,3]triazole-4-carbonyl)-amino]-pyridin-3-yl}-benzoic acid methyl ester;    4-Chloro-3-{6-[(4-methyl-isothiazole-5-carbonyl)-amino]-pyridin-3-yl}-benzoic acid methyl ester;    4-Chloro-3-{6-[(4-methyl-thiazole-5-carbonyl)-amino]-pyridin-3-yl}-benzoic acid methyl ester;    4-Chloro-3-{6-[(4-methyl-oxazole-5-carbonyl)-amino]-pyridin-3-yl}-benzoic acid methyl ester;    4-Chloro-3-{6-[(2-methyl-2H-pyrazole-3-carbonyl)-amino]-pyridin-3-yl}-benzoic acid methyl ester;    4-Chloro-3-{6-[(4-fluoro-isothiazole-5-carbonyl)-amino]-pyridin-3-yl}-benzoic acid methyl ester;    3-Methyl-N-[5-(2-methyl-5-oxazol-2-yl-phenyl)-pyridin-2-yl]-isonicotinamide;    3-Methyl-N-[6-(2-methyl-5-oxazol-2-yl-phenyl)-pyridin-3-yl]-isonicotinamide;    2,6-Difluoro-N-[5-methyl-6-(3-oxazol-2-yl-phenyl)-pyridin-3-yl]-benzamide;    2,6-Difluoro-N-[4-methyl-5-(3-oxazol-2-yl-phenyl)-pyridin-2-yl]-benzamide;    2,6-Difluoro-N-[6-methyl-5-(3-oxazol-2-yl-phenyl)-pyridin-2-yl]-benzamide;    2,6-Difluoro-N-[5-(2-methyl-5-thiazol-2-yl-phenyl)-pyridin-2-yl]-benzamide;    3-Methyl-N-[5-(2-methyl-5-thiazol-2-yl-phenyl)-pyridin-2-yl]-isonicotinamide;    3-Methyl-N-[6-(2-methyl-5-thiazol-2-yl-phenyl)-pyridin-3-yl]-isonicotinamide;    2,6-Difluoro-N-[6-(2-methyl-5-thiazol-2-yl-phenyl)-pyridin-3-yl]-benzamide;    2,6-Difluoro-N-[6-(2-methyl-5-thiazol-2-yl-phenyl)-pyridin-3-yl]-benzamide hydrochloride;    N-[5-(2-Chloro-5-thiazol-2-yl-phenyl)-pyridin-2-yl]-3-methyl-isonicotinamide;    N-[6-(2-Chloro-5-thiazol-2-yl-phenyl)-pyridin-3-yl]-3-methyl-isonicotinamide;    N-[6-(2-Chloro-5-thiazol-2-yl-phenyl)-pyridin-3-yl]-2,6-difluoro-benzamide;    3-[5-(2,6-Difluoro-benzoylamino)-pyridin-2-yl]-4-methyl-benzoic acid ethyl ester;    3-[6-(2,6-Difluoro-benzoylamino)-pyridin-3-yl]-4-methyl-benzoic acid ethyl ester;    2,6-Difluoro-N-[5-(2-methyl-5-oxazol-5-yl-phenyl)-pyridin-2-yl]-benzamide;    2,6-Difluoro-N-[6-(2-methyl-5-oxazol-5-yl-phenyl)-pyridin-3-yl]-benzamide;    2,6-Difluoro-N-[6-(5-isoxazol-5-yl-2-methyl-phenyl)-pyridin-3-yl]-benzamide;    2,6-Difluoro-N-[5-(5-isoxazol-5-yl-2-methyl-phenyl)-pyridin-2-yl]-benzamide;    2,6-Difluoro-N-{5-[2-methyl-5-(3-methyl-isoxazol-5-yl)-phenyl]-pyridin-2-yl}-benzamide;    2,6-Difluoro-N-{6-[2-methyl-5-(3-methyl-isoxazol-5-yl)-phenyl]-pyridin-3-yl}-benzamide;    2,6-Difluoro-N-[6-(2-methyl-5-pyridin-3-yl-phenyl)-pyridin-3-yl]-benzamide;    2,6-Difluoro-N-[6-(2-methyl-5-pyridin-2-yl-phenyl)-pyridin-3-yl]-benzamide;    2,6-Difluoro-N-[5-(2-methyl-5-[1,3,4]oxadiazol-2-yl-phenyl)-pyridin-2-yl]-benzamide;    2,6-Difluoro-N-[5-(2-methyl-5-[1,3,4]thiadiazol-2-yl-phenyl)-pyridin-2-yl]-benzamide;    4-Chloro-3-[6-(2,6-difluoro-benzoylamino)-pyridin-3-yl]-benzoic acid propyl ester;    4-Chloro-3-[6-(2,6-difluoro-benzoylamino)-pyridin-3-yl]-benzoic acid 2-methoxy-ethyl ester;    2,6-Difluoro-N-[5-(5-furan-2-yl-2-methyl-phenyl)-pyridin-2-yl]-benzamide;    2,6-Difluoro-N-[5-(2-methyl-5-thiophen-2-yl-phenyl)-pyridin-2-yl]-benzamide;    2,6-Difluoro-N-[5-(5-furan-3-yl-2-methyl-phenyl)-pyridin-2-yl]-benzamide;    2,6-Difluoro-N-[5-(2-methyl-5-thiophen-3-yl-phenyl)-pyridin-2-yl]-benzamide;    N-(5-(2-methoxy-5-(oxazol-5-yl)phenyl)pyridin-2-yl)-4-methyl-1,2,3-thiadiazole-5-carboxamide;    N-(5-(5-(isoxazol-5-yl)-2-methylphenyl)pyridin-2-yl)-4-methyl-1,2,3-thiadiazole-5-carboxamide    2,6-difluoro-N-(5-(2-methyl-5-(1,3,4-oxadiazol-2-yl)phenyl)pyridin-2-yl)benzamide;    2,6-difluoro-N-(5-(2-methyl-5-(oxazol-5-yl)phenyl)pyridin-2-yl)benzamide;    N-(5-(2-chloro-5-(1,3,4-oxadiazol-2-yl)phenyl)pyridin-2-yl)-2,6-difluorobenzamide;    N-(6-(2-chloro-5-(thiazol-2-yl)phenyl)pyridin-3-yl)-2,6-difluorobenzamide;    N-(6-(2-chloro-5-(thiazol-2-yl)phenyl)pyridin-3-yl)-2,6-difluorobenzamide hydrochloric acid salt;    2,6-Difluoro-N-(6-(2-methyl-5-(thiazol-2-yl)phenyl)pyridin-3-yl)benzamide;    2,6-Difluoro-N-(6-(2-methyl-5-(1,3,4-oxadiazol-2-yl)phenyl)pyridin-3-yl)benzamide;    N-(6-(2-chloro-5-(oxazol-2-yl)phenyl)pyridin-3-yl)-2,6-difluorobenzamide;    N-(6-(2-chloro-5-(oxazol-2-yl)phenyl)pyridin-3-yl)-2,6-difluorobenzamide hydrochloric acid salt;    2,6-Difluoro-N-(6-(2-methyl-5-(oxazol-5-yl)phenyl)pyridin-3-yl)benzamide;    2,6-Difluoro-N-(6-(2-methyl-5-(oxazol-5-yl)phenyl)pyridin-3-yl)benzamide hydrochloric acid salt; or    4-chloro-2-fluoro-N-(6-(2-methyl-5-(oxazol-2-yl)phenyl)pyridin-3-yl)benzamide; 
 or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof.  
   
   
   
       27 . A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound of  claim 1  or  claim 26 .  
   
   
       28 . The pharmaceutical composition of  claim 27 , further comprising one or more additional therapeutic agents.  
   
   
       29 . (canceled)  
   
   
       30 . The pharmaceutical composition of  claim 28 , wherein the additional therapeutic agent is selected from the group consisting of steroids, non-steroidal anti-inflammatory agents, antihistamines, analgesics, and suitable mixtures thereof.  
   
   
       31 .- 56 . (canceled)  
   
   
       57 . A method of inhibiting immune cell activation comprising administering to the cell a compound represented by structural formula (I):  
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein:  
       Y is a monocyclic optionally substituted aryl or a monocyclic optionally substituted heteroaryl;  
       L is a linker selected from the group consisting of —NRCR 2 —, —CR 2 NR—, —C(O)—, —NR—C(O)—, —C(O)—NR—, —OC(O)—, —C(O)O—, —C(S)—, —NR—C(S)—, —C(S)—NR—;  
       one of X 1  or X 2  is CH or CZ and the other is N;  
       each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, —S(O) p -alkyl, —C(O)NRR, —(CH 2 ) k NRR, —(CH 2 ) k OR, —(CH 2 ) k SR, cyano, nitro, or lower haloalkoxy;  
       R, for each occurrence is independently selected from —H or an alkyl;  
       R 3  is H, an alkyl, a haloalkyl, a halo, a haloalkoxy, —OR 5 , —SR 5 , or —NR 6 R 7 ;  
       R 4  is a halo, a haloalkyl, cyano, nitro, —C(O)R 5 , —C(O)OR 5 , —C(O)SR 5 , —C(O)NR 9 R 10 , —C(S)R 5 , —C(S)OR 5 , —C(S)SR 5 , —C(S)NR 6 R 7 , —C(NR 8 )R 5 , —C(NR 8 )OR 5 , —C(NR 8 )SR 5 , —C(NR 8 )NR 6 R 7 , —S(O) p R 5 , —S(O) p NR 5 , —S(O) p OR 5 , —P(O)(OR 5 ) 2 , —OP(O)(OR 5 ) 2 , —P(O)(R 5 ) 2 , an optionally substituted heterocyclyl, or an optionally substituted heteroaryl;  
       R 5 , for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;  
       R 6  and R 7 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 6  and R 7  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       R 8 , for each occurrence, is independently —H, a halo, an alkyl, —OR 5 , —NR 6 R 7 , —C(O)R 5 , —C(O)OR 5 , or —C(O)NR 6 R 7 ;  
       R 9  and R 10 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted 5- to 14-membered cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, or an optionally substituted heteroaryl selected from the group consisting of an optionally substituted pyridinyl, an optionally substituted thienyl, an optionally substituted pyrrolyl, an optionally substituted oxazolyl, an optionally substituted imidazolyl, an optionally substituted indolizinyl, an optionally substituted isoxazolyl, an optionally substituted pyrazolyl, an optionally substituted isothiazolyl, an optionally substituted pyridazinyl, an optionally substituted pyrimidinyl, an optionally substituted pyrazinyl, an optionally substituted triazinyl, an optionally substituted triazolyl, an optionally substituted pyridinyl, an optionally substituted thiadiazolyl, an optionally substituted pyrazinyl, an optionally substituted quinolinyl, an optionally substituted isoquniolinyl, an optionally substituted indazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzofuryl, an optionally substituted benzothiazolyl, an optionally substituted indolizinyl, an optionally substituted imidazopyridinyl, an optionally substituted tetrazolyl, an optionally substituted benzimidazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzothiazolyl, an optionally substituted benzothiadiazolyl, an optionally substituted benzoxadiazolyl, an optionally substituted indolyl, an optionally substituted tetrahydroindolyl, an optionally substituted azaindolyl, an optionally substituted imidazopyridyl, an optionally substituted qunizaolinyl, an optionally substituted purinyl, an optionally substituted pyrrolo[2,3]pyrimidyl, an optionally substituted pyrazolo[3,4]pyrimidyl or an optionally substituted benzo(b)thienyl; or R 9  and R 10  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       q, for each occurrence, is independently, an integer from 1 to 3;  
       k is for each occurrence, is independently, an integer from 1 to 4;  
       n is zero, 1 or 2; and  
       p, for each occurrence, is independently 1 or 2.  
     
   
   
       58 . The method of  claim 57 , wherein immune cell activation is inhibited in a subject by administering the compound to the subject.  
   
   
       59 . The method of  claim 58 , wherein the subject is human.  
   
   
       60 . A method of inhibiting cytokine production in a cell, comprising administering to the cell a compound represented by structural formula (I):  
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein:  
       Y is a monocyclic optionally substituted aryl or a monocyclic optionally substituted heteroaryl;  
       L is a linker selected from the group consisting of —NRCR 2 —, —CR 2 NR—, —C(O)—, —NR—C(O)—, —C(O)—NR—, —OC(O)—, —C(O)O—, —C(S)—, —NR—C(S)—, —C(S)—NR—;  
       one of X 1  or X 2  is CH or CZ and the other is N;  
       each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, —S(O) p -alkyl, —C(O)NRR, —(CH 2 ) k NRR, —(CH 2 ) k OR, —(CH 2 ) k SR, cyano, nitro, or lower haloalkoxy;  
       R, for each occurrence is independently selected from —H or an alkyl;  
       R 3  is H, an alkyl, a haloalkyl, a halo, a haloalkoxy, —OR 5 , —SR 5 , or —NR 6 R 7 ;  
       R 4  is a halo, a haloalkyl, cyano, nitro, —C(O)R 5 , —C(O)OR 5 , —C(O)SR 5 , —C(O)NR 9 R 10 , —C(S)R 5 , —C(S)OR 5 , —C(S)SR 5 , —C(S)NR 6 R 7 , —C(NR 8 )R 5 , —C(NR 8 )OR 5 , —C(NR 8 )SR 5 , —C(NR 8 )NR 6 R 7 , —S(O) p R 5 , —S(O) p NR 5 , —S(O) p OR 5 , —P(O)(OR 5 ) 2 , —OP(O)(OR 5 ) 2 , —P(O)(R 5 ) 2 , an optionally substituted heterocyclyl, or an optionally substituted heteroaryl;  
       R 5 , for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;  
       R 6  and R 7 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 6  and R 7  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       R 8 , for each occurrence, is independently —H, a halo, an alkyl, —OR 5 , —NR 6 R 7 , —C(O)R 5 , —C(O)OR 5 , or —C(O)NR 6 R 7 ;  
       R 9  and R 10 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted 5- to 14-membered cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, or an optionally substituted heteroaryl selected from the group consisting of an optionally substituted pyridinyl, an optionally substituted thienyl, an optionally substituted pyrrolyl, an optionally substituted oxazolyl, an optionally substituted imidazolyl, an optionally substituted indolizinyl, an optionally substituted isoxazolyl, an optionally substituted pyrazolyl, an optionally substituted isothiazolyl, an optionally substituted pyridazinyl, an optionally substituted pyrimidinyl, an optionally substituted pyrazinyl, an optionally substituted triazinyl, an optionally substituted triazolyl, an optionally substituted pyridinyl, an optionally substituted thiadiazolyl, an optionally substituted pyrazinyl, an optionally substituted quinolinyl, an optionally substituted isoquniolinyl, an optionally substituted indazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzofuryl, an optionally substituted benzothiazolyl, an optionally substituted indolizinyl, an optionally substituted imidazopyridinyl, an optionally substituted tetrazolyl, an optionally substituted benzimidazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzothiazolyl, an optionally substituted benzothiadiazolyl, an optionally substituted benzoxadiazolyl, an optionally substituted indolyl, an optionally substituted tetrahydroindolyl, an optionally substituted azaindolyl, an optionally substituted imidazopyridyl, an optionally substituted qunizaolinyl, an optionally substituted purinyl, an optionally substituted pyrrolo[2,3]pyrimidyl, an optionally substituted pyrazolo[3,4]pyrimidyl or an optionally substituted benzo(b)thienyl; or R 9  and R 10  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       q, for each occurrence, is independently, an integer from 1 to 3;  
       k is for each occurrence, is independently, an integer from 1 to 4;  
       n is zero, 1 or 2; and  
       p, for each occurrence, is independently 1 or 2.  
     
   
   
       61 . The method of  claim 60 , wherein cytokine production is inhibited in a subject by administering the compound to the subject.  
   
   
       62 . The method of  claim 61 , wherein the subject is human.  
   
   
       63 . The method of  claim 61 , wherein the cytokine is selected from the group consisting of IL-2, IL-4, IL-5, IL-13, GM-CSF, IFN-γ, TNF-α, and combinations thereof.  
   
   
       64 . The method of  claim 63 , wherein the cytokine is IL-2.  
   
   
       65 . A method of modulating an ion channel in a cell, wherein the ion channel is involved in immune cell activation, comprising administering to the cell a compound represented by structural formula (I):  
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein:  
       Y is a monocyclic optionally substituted aryl or a monocyclic optionally substituted heteroaryl;  
       L is a linker selected from the group consisting of —NRCR 2 —, —CR 2 NR—, —C(O)—, —NR—C(O)—, —C(O)—NR—, —OC(O)—, —C(O)O—, —C(S)—, —NR—C(S)—, —C(S)—NR—;  
       one of X 1  or X 2  is CH or CZ and the other is N;  
       each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, —S(O) p -alkyl, —C(O)NRR, —(CH 2 ) k NRR, —(CH 2 ) k OR, —(CH 2 ) k SR, cyano, nitro, or lower haloalkoxy;  
       R, for each occurrence is independently selected from —H or an alkyl;  
       R 3  is H, an alkyl, a haloalkyl, a halo, a haloalkoxy, —OR 5 , —SR 5 , or —NR 6 R 7 ;  
       R 4  is a halo, a haloalkyl, cyano, nitro, —C(O)R 5 , —C(O)OR 5 , —C(O)SR 5 , —C(O)NR 9 R 10 , —C(S)R 5 , —C(S)OR 5 , —C(S)SR 5 , —C(S)NR 6 R 7 , —C(NR 8 )R 5 , —C(NR 8 )OR 5 , —C(NR 8 )SR 5 , —C(NR 8 )NR 6 R 7 , —S(O) p R 5 , —S(O) p NR 5 , —S(O) p OR 5 , —P(O)(OR 5 ) 2 , —OP(O)(OR 5 ) 2 , —P(O)(R 5 ) 2 , an optionally substituted heterocyclyl, or an optionally substituted heteroaryl;  
       R 5 , for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;  
       R 6  and R 7 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 6  and R 7  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       R 8 , for each occurrence, is independently —H, a halo, an alkyl, —OR 5 , —NR 6 R 7 , —C(O)R 5 , —C(O)OR 5 , or —C(O)NR 6 R 7 ;  
       R 9  and R 10 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted 5- to 14-membered cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, or an optionally substituted heteroaryl selected from the group consisting of an optionally substituted pyridinyl, an optionally substituted thienyl, an optionally substituted pyrrolyl, an optionally substituted oxazolyl, an optionally substituted imidazolyl, an optionally substituted indolizinyl, an optionally substituted isoxazolyl, an optionally substituted pyrazolyl, an optionally substituted isothiazolyl, an optionally substituted pyridazinyl, an optionally substituted pyrimidinyl, an optionally substituted pyrazinyl, an optionally substituted triazinyl, an optionally substituted triazolyl, an optionally substituted pyridinyl, an optionally substituted thiadiazolyl, an optionally substituted pyrazinyl, an optionally substituted quinolinyl, an optionally substituted isoquniolinyl, an optionally substituted indazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzofuryl, an optionally substituted benzothiazolyl, an optionally substituted indolizinyl, an optionally substituted imidazopyridinyl, an optionally substituted tetrazolyl, an optionally substituted benzimidazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzothiazolyl, an optionally substituted benzothiadiazolyl, an optionally substituted benzoxadiazolyl, an optionally substituted indolyl, an optionally substituted tetrahydroindolyl, an optionally substituted azaindolyl, an optionally substituted imidazopyridyl, an optionally substituted qunizaolinyl, an optionally substituted purinyl, an optionally substituted pyrrolo[2,3]pyrimidyl, an optionally substituted pyrazolo[3,4]pyrimidyl or an optionally substituted benzo(b)thienyl; or R 9  and R 10  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       q, for each occurrence, is independently, an integer from 1 to 3;  
       k is for each occurrence, is independently, an integer from 1 to 4;  
       n is zero, 1 or 2; and  
       p, for each occurrence, is independently 1 or 2.  
     
   
   
       66 . The method of  claim 65 , wherein the ion channel is in a subject and it is modulated by administering the compound to the subject.  
   
   
       67 . The method of  claim 66 , wherein the subject is human.  
   
   
       68 . The method of  claim 66 , wherein the ion channel is a Ca 2+ -release-activated Ca 2+  channel (CRAC).  
   
   
       69 . A method of inhibiting T-cell and/or B-cell proliferation in response to an antigen, comprising administering to the cell a compound represented by structural formula (I):  
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein:  
       Y is a monocyclic optionally substituted aryl or a monocyclic optionally substituted heteroaryl;  
       L is a linker selected from the group consisting of —NRCR 2 —, —CR 2 NR—, —C(O)—, —NR—C(O)—, —C(O)—NR—, —OC(O)—, —C(O)O—, —C(S)—, —NR—C(S)—, —C(S)—NR—;  
       one of X 1  or X 2  is CH or CZ and the other is N;  
       each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, —S(O) p -alkyl, —C(O)NRR, —(CH 2 ) k NRR, —(CH 2 ) k OR, —(CH 2 ) k SR, cyano, nitro, or lower haloalkoxy;  
       R, for each occurrence is independently selected from —H or an alkyl;  
       R 3  is H, an alkyl, a haloalkyl, a halo, a haloalkoxy, —OR 5 , —SR 5 , or —NR 6 R 7 ;  
       R 4  is a halo, a haloalkyl, cyano, nitro, —C(O)R 5 , —C(O)OR 5 , —C(O)SR 5 , —C(O)NR 9 R 10 , —C(S)R 5 , —C(S)OR 5 , —C(S)SR 5 , —C(S)NR 6 R 7 , —C(NR 8 )R 5 , —C(NR 8 )OR 5 , —C(NR 8 )SR 5 , —C(NR 8 )NR 6 R 7 , —S(O) p R 5 , —S(O) p NR 5 , —S(O) p OR 5 , —P(O)(OR 5 ) 2 , —OP(O)(OR 5 ) 2 , —P(O)(R 5 ) 2 , an optionally substituted heterocyclyl, or an optionally substituted heteroaryl;  
       R 5 , for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;  
       R 6  and R 7 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 6  and R 7  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       R 8 , for each occurrence, is independently —H, a halo, an alkyl, —OR 5 , —NR 6 R 7 , —C(O)R 5 , —C(O)OR 5 , or —C(O)NR 6 R 7 ;  
       R 9  and R 10 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted 5- to 14-membered cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, or an optionally substituted heteroaryl selected from the group consisting of an optionally substituted pyridinyl, an optionally substituted thienyl, an optionally substituted pyrrolyl, an optionally substituted oxazolyl, an optionally substituted imidazolyl, an optionally substituted indolizinyl, an optionally substituted isoxazolyl, an optionally substituted pyrazolyl, an optionally substituted isothiazolyl, an optionally substituted pyridazinyl, an optionally substituted pyrimidinyl, an optionally substituted pyrazinyl, an optionally substituted triazinyl, an optionally substituted triazolyl, an optionally substituted pyridinyl, an optionally substituted thiadiazolyl, an optionally substituted pyrazinyl, an optionally substituted quinolinyl, an optionally substituted isoquniolinyl, an optionally substituted indazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzofuryl, an optionally substituted benzothiazolyl, an optionally substituted indolizinyl, an optionally substituted imidazopyridinyl, an optionally substituted tetrazolyl, an optionally substituted benzimidazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzothiazolyl, an optionally substituted benzothiadiazolyl, an optionally substituted benzoxadiazolyl, an optionally substituted indolyl, an optionally substituted tetrahydroindolyl, an optionally substituted azaindolyl, an optionally substituted imidazopyridyl, an optionally substituted qunizaolinyl, an optionally substituted purinyl, an optionally substituted pyrrolo[2,3]pyrimidyl, an optionally substituted pyrazolo[3,4]pyrimidyl or an optionally substituted benzo(b)thienyl; or R 9  and R 10  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       q, for each occurrence, is independently, an integer from 1 to 3;  
       k is for each occurrence, is independently, an integer from 1 to 4;  
       n is zero, 1 or 2; and  
       p, for each occurrence, is independently 1 or 2.  
     
   
   
       70 . The method of  claim 69 , wherein T-cell and/or B-cell proliferation is inhibited in a subject by administering the compound to the subject.  
   
   
       71 . The method of  claim 70 , wherein the subject is human.  
   
   
       72 . A method for treating or preventing an immune disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound represented by structural formula (I):  
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein:  
       Y is a monocyclic optionally substituted aryl or a monocyclic optionally substituted heteroaryl;  
       L is a linker selected from the group consisting of —NRCR 2 —, —CR 2 NR—, —C(O)—, —NR—C(O)—, —C(O)—NR—, —OC(O)—, —C(O)O—, —C(S)—, —NR—C(S)—, —C(S)—NR—;  
       one of X 1  or X 2  is CH or CZ and the other is N;  
       each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, —S(O) p -alkyl, —C(O)NRR, —(CH 2 ) k NRR, —(CH 2 ) k OR, —(CH 2 ) k SR, cyano, nitro, or lower haloalkoxy;  
       R, for each occurrence is independently selected from —H or an alkyl;  
       R 3  is H, an alkyl, a haloalkyl, a halo, a haloalkoxy, —OR 5 , —SR 5 , or —NR 6 R 7 ;  
       R 4  is a halo, a haloalkyl, cyano, nitro, —C(O)R 5 , —C(O)OR 5 , —C(O)SR 5 , —C(O)NR 9 R 10 , —C(S)R 5 , —C(S)OR 5 , —C(S)SR 5 , —C(S)NR 6 R 7 , —C(NR 8 )R 5 , —C(NR 8 )OR 5 , —C(NR 8 )SR 5 , —C(NR 8 )NR 6 R 7 , —S(O) p R 5 , —S(O) p NR 5 , —S(O) p OR 5 , —P(O)(OR 5 ) 2 , —OP(O)(OR 5 ) 2 , —P(O)(R 5 ) 2 , an optionally substituted heterocyclyl, or an optionally substituted heteroaryl;  
       R 5 , for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;  
       R 6  and R 7 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 6  and R 7  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       R 8 , for each occurrence, is independently —H, a halo, an alkyl, —OR 5 , —NR 6 R 7 , —C(O)R 5 , —C(O)OR 5 , or —C(O)NR 6 R 7 ;  
       R 9  and R 10 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted 5- to 14-membered cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, or an optionally substituted heteroaryl selected from the group consisting of an optionally substituted pyridinyl, an optionally substituted thienyl, an optionally substituted pyrrolyl, an optionally substituted oxazolyl, an optionally substituted imidazolyl, an optionally substituted indolizinyl, an optionally substituted isoxazolyl, an optionally substituted pyrazolyl, an optionally substituted isothiazolyl, an optionally substituted pyridazinyl, an optionally substituted pyrimidinyl, an optionally substituted pyrazinyl, an optionally substituted triazinyl, an optionally substituted triazolyl, an optionally substituted pyridinyl, an optionally substituted thiadiazolyl, an optionally substituted pyrazinyl, an optionally substituted quinolinyl, an optionally substituted isoquniolinyl, an optionally substituted indazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzofuryl, an optionally substituted benzothiazolyl, an optionally substituted indolizinyl, an optionally substituted imidazopyridinyl, an optionally substituted tetrazolyl, an optionally substituted benzimidazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzothiazolyl, an optionally substituted benzothiadiazolyl, an optionally substituted benzoxadiazolyl, an optionally substituted indolyl, an optionally substituted tetrahydroindolyl, an optionally substituted azaindolyl, an optionally substituted imidazopyridyl, an optionally substituted qunizaolinyl, an optionally substituted purinyl, an optionally substituted pyrrolo[2,3]pyrimidyl, an optionally substituted pyrazolo[3,4]pyrimidyl or an optionally substituted benzo(b)thienyl; or R 9  and R 10  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       q, for each occurrence, is independently, an integer from 1 to 3;  
       k is for each occurrence, is independently, an integer from 1 to 4;  
       n is zero, 1 or 2; and  
       p, for each occurrence, is independently 1 or 2.  
     
   
   
       73 . The method of  claim 72 , wherein the subject is human.  
   
   
       74 . The method of  claim 72 , wherein the disorder is selected from the group consisting of multiple sclerosis, myasthenia gravis, Guillain-Barré, autoimmune uveitis, autoimmune hemolytic anemia, pernicious anemia, autoimmune thrombocytopenia, temporal arteritis, anti-phospholipid syndrome, vasculitides such as Wegener's granulomatosis, Behcet's disease, psoriasis, dermatitis herpetiformis, pemphigus vulgaris, vitiligo, Crohn's disease, ulcerative colitis, primary biliary cirrhosis, autoimmune hepatitis, Type 1 or immune-mediated diabetes mellitus, Grave's disease. Hashimoto's thyroiditis, autoimmune oophoritis and orchitis, autoimmune disorder of the adrenal gland, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis, dermatomyositis, ankylosing spondylitis, and Sjogren's syndrome.  
   
   
       75 . A method for treating or preventing an inflammatory condition in a subject in need thereof, comprising administering to the subject an effective amount of a compound represented by structural formula (I):  
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein:  
       Y is a monocyclic optionally substituted aryl or a monocyclic optionally substituted heteroaryl;  
       L is a linker selected from the group consisting of —NRCR 2 —, —CR 2 NR—, —C(O)—, —NR—C(O)—, —C(O)—NR—, —OC(O)—, —C(O)O—, —C(S)—, —NR—C(S)—, —C(S)—NR—;  
       one of X 1  or X 2  is CH or CZ and the other is N;  
       each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, —S(O) p -alkyl, —C(O)NRR, —(CH 2 ) k NRR, —(CH 2 ) k OR, —(CH 2 ) k SR, cyano, nitro, or lower haloalkoxy;  
       R, for each occurrence is independently selected from —H or an alkyl;  
       R 3  is H, an alkyl, a haloalkyl, a halo, a haloalkoxy, —OR 5 , —SR 5 , or —NR 6 R 7 ;  
       R 4  is a halo, a haloalkyl, cyano, nitro, —C(O)R 5 , —C(O)OR 5 , —C(O)SR 5 , —C(O)NR 9 R 10 , —C(S)R 5 , —C(S)OR 5 , —C(S)SR 5 , —C(S)NR 6 R 7 , —C(NR 8 )R 5 , —C(NR 8 )OR 5 , —C(NR 8 )SR 5 , —C(NR 8 )NR 6 R 7 , —S(O) p R 5 , —S(O) p NR 5 , —S(O) p OR 5 , —P(O)(OR 5 ) 2 , —OP(O)(OR 5 ) 2 , —P(O)(R 5 ) 2 , an  
       optionally substituted heterocyclyl, or an optionally substituted heteroaryl;  
       R 5 , for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;  
       R 6  and R 7 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 6  and R 7  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       R 8 , for each occurrence, is independently —H, a halo, an alkyl, —OR 5 , —NR 6 R 7 , —C(O)R 5 , —C(O)OR 5 , or —C(O)NR 6 R 7 ;  
       R 9  and R 10 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted 5- to 14-membered cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, or an optionally substituted heteroaryl selected from the group consisting of an optionally substituted pyridinyl, an optionally substituted thienyl, an optionally substituted pyrrolyl, an optionally substituted oxazolyl, an optionally substituted imidazolyl, an optionally substituted indolizinyl, an optionally substituted isoxazolyl, an optionally substituted pyrazolyl, an optionally substituted isothiazolyl, an optionally substituted pyridazinyl, an optionally substituted pyrimidinyl, an optionally substituted pyrazinyl, an optionally substituted triazinyl, an optionally substituted triazolyl, an optionally substituted pyridinyl, an optionally substituted thiadiazolyl, an optionally substituted pyrazinyl, an optionally substituted quinolinyl, an optionally substituted isoquniolinyl, an optionally substituted indazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzofuryl, an optionally substituted benzothiazolyl, an optionally substituted indolizinyl, an optionally substituted imidazopyridinyl, an optionally substituted tetrazolyl, an optionally substituted benzimidazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzothiazolyl, an optionally substituted benzothiadiazolyl, an optionally substituted benzoxadiazolyl, an optionally substituted indolyl, an optionally substituted tetrahydroindolyl, an optionally substituted azaindolyl, an optionally substituted imidazopyridyl, an optionally substituted qunizaolinyl, an optionally substituted purinyl, an optionally substituted pyrrolo[2,3]pyrimidyl, an optionally substituted pyrazolo[3,4]pyrimidyl or an optionally substituted benzo(b)thienyl; or R 9  and R 10  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       q, for each occurrence, is independently, an integer from 1 to 3;  
       k is for each occurrence, is independently, an integer from 1 to 4;  
       n is zero, 1 or 2; and  
       p, for each occurrence, is independently 1 or 2.  
     
   
   
       76 . The method of  claim 75 , wherein the subject is human.  
   
   
       77 . The method according to  claim 75 , wherein the disorder is selected from transplant rejection, skin graft rejection, arthritis, rheumatoid arthritis, osteoarthritis and bone diseases associated with increased bone resorption; inflammatory bowel disease, ileitis, ulcerative colitis, Barrett's syndrome, Crohn's disease; asthma, adult respiratory distress syndrome, chronic obstructive airway disease; corneal dystrophy, trachoma, onchocerciasis, uveitis, sympathetic ophthalmitis, endophthalmitis; gingivitis, periodontitis; tuberculosis; leprosy; uremic complications, glomerulonephritis, nephrosis; sclerodermatitis, psoriasis, eczema; chronic demyelinating diseases of the nervous system, multiple sclerosis, AIDS-related neurodegeneration, Alzheimer's disease, infectious meningitis, encephalomyelitis, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis viral or autoimmune encephalitis; autoimmune disorders, immune-complex vasculitis, systemic lupus and erythematodes; systemic lupus erythematosus (SLE); cardiomyopathy, ischemic heart disease hypercholesterolemia, atherosclerosis, preeclampsia; chronic liver failure, brain and spinal cord trauma, and cancer.  
   
   
       78 . A method for suppressing the immune system of a subject in need thereof, comprising administering to the subject an effective amount of a compound represented by structural formula (I):  
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein:  
       Y is a monocyclic optionally substituted aryl or a monocyclic optionally substituted heteroaryl;  
       L is a linker selected from the group consisting of —NRCR 2 —, —CR 2 NR—, —C(O)—, —NR—C(O)—, —C(O)—NR—, —OC(O)—, —C(O)O—, —C(S)—, —NR—C(S)—, —C(S)—NR—;  
       one of X 1  or X 2  is CH or CZ and the other is N;  
       each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, —S(O) p -alkyl, —C(O)NRR, —(CH 2 ) k NRR, —(CH 2 ) k OR, —(CH 2 ) k SR, cyano, nitro, or lower haloalkoxy;  
       R, for each occurrence is independently selected from —H or an alkyl;  
       R 3  is H, an alkyl, a haloalkyl, a halo, a haloalkoxy, —OR 5 , —SR 5 , or —NR 6 R 7 ;  
       R 4  is a halo, a haloalkyl, cyano, nitro, —C(O)R 5 , —C(O)OR 5 , —C(O)SR 5 , —C(O)NR 9 R 10 , —C(S)R 5 , —C(S)OR 5 , —C(S)SR 5 , —C(S)NR 6 R 7 , —C(NR 8 )R 5 , —C(NR 8 )OR 5 , —C(NR 8 )SR 5 , —C(NR 8 )NR 6 R 7 , —S(O) p R 5 , —S(O) p NR 5 , —S(O) p OR 5 , —P(O)(OR 5 ) 2 , —OP(O)(OR 5 ) 2 , —P(O)(R 5 ) 2 , an optionally substituted heterocyclyl, or an optionally substituted heteroaryl;  
       R 5 , for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;  
       R 6  and R 7 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 6  and R 7  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       R 8 , for each occurrence, is independently —H, a halo, an alkyl, —OR 5 , —NR 6 R 7 , —C(O)R 5 , —C(O)OR 5 , or —C(O)NR 6 R 7 ;  
       R 9  and R 10 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted 5- to 14-membered cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, or an optionally substituted heteroaryl selected from the group consisting of an optionally substituted pyridinyl, an optionally substituted thienyl, an optionally substituted pyrrolyl, an optionally substituted oxazolyl, an optionally substituted imidazolyl, an optionally substituted indolizinyl, an optionally substituted isoxazolyl, an optionally substituted pyrazolyl, an optionally substituted isothiazolyl, an optionally substituted pyridazinyl, an optionally substituted pyrimidinyl, an optionally substituted pyrazinyl, an optionally substituted triazinyl, an optionally substituted triazolyl, an optionally substituted pyridinyl, an optionally substituted thiadiazolyl, an optionally substituted pyrazinyl, an optionally substituted quinolinyl, an optionally substituted isoquniolinyl, an optionally substituted indazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzofuryl, an optionally substituted benzothiazolyl, an optionally substituted indolizinyl, an optionally substituted imidazopyridinyl, an optionally substituted tetrazolyl, an optionally substituted benzimidazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzothiazolyl, an optionally substituted benzothiadiazolyl, an optionally substituted benzoxadiazolyl, an optionally substituted indolyl, an optionally substituted tetrahydroindolyl, an optionally substituted azaindolyl, an optionally substituted imidazopyridyl, an optionally substituted qunizaolinyl, an optionally substituted purinyl, an optionally substituted pyrrolo[2,3]pyrimidyl, an optionally substituted pyrazolo[3,4]pyrimidyl or an optionally substituted benzo(b)thienyl; or R 9  and R 10  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       q, for each occurrence, is independently, an integer from 1 to 3;  
       k is for each occurrence, is independently, an integer from 1 to 4;  
       n is zero, 1 or 2; and  
       p, for each occurrence, is independently 1 or 2.  
     
   
   
       79 . The method of  claim 78 , wherein the subject is human.  
   
   
       80 . A method for treating or preventing an allergic disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound represented by structural formula (I):  
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein:  
       Y is a monocyclic optionally substituted aryl or a monocyclic optionally substituted heteroaryl;  
       L is a linker selected from the group consisting of —NRCR 2 —, —CR 2 NR—, —C(O)—, —NR—C(O)—, —C(O)—NR—, —OC(O)—, —C(O)O—, —C(S)—, —NR—C(S)—, —C(S)—NR—;  
       one of X 1  or X 2  is CH or CZ and the other is N;  
       each Z is independently selected from the group consisting of a lower alkyl, a lower haloalkyl, a halo, a lower alkoxy, a lower alkyl sufanyl, —S(O) p -alkyl, —C(O)NRR, —(CH 2 ) k NRR, —(CH 2 ) k OR, —(CH 2 ) k SR, cyano, nitro, or lower haloalkoxy;  
       R, for each occurrence is independently selected from —H or an alkyl;  
       R 3  is H, an alkyl, a haloalkyl, a halo, a haloalkoxy, —OR 5 , —SR 5 , or —NR 6 R 7 ;  
       R 4  is a halo, a haloalkyl, cyano, nitro, —C(O)R 5 , —C(O)OR 5 , —C(O)SR 5 , —C(O)NR 9 R 10 , —C(S)R 5 , —C(S)OR 5 , —C(S)SR 5 , —C(S)NR 6 R 7 , —C(NR 8 )R 5 , —C(NR 8 )OR 5 , —C(NR 8 )SR 5 , —C(NR 8 )NR 6 R 7 , —S(O) p R 5 , —S(O) p NR 5 , —S(O) p OR 5 , —P(O)(OR 5 ) 2 , —OP(O)(OR 5 ) 2 , —P(O)(R 5 ) 2 , an optionally substituted heterocyclyl, or an optionally substituted heteroaryl;  
       R 5 , for each occurrence, is independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl;  
       R 6  and R 7 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteraralkyl; or R 6  and R 7  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       R 8 , for each occurrence, is independently —H, a halo, an alkyl, —OR 5 , —NR 6 R 7 , —C(O)R 5 , —C(O)OR 5 , or —C(O)NR 6 R 7 ;  
       R 9  and R 10 , for each occurrence are, independently, H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted 5- to 14-membered cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted heteraralkyl, or an optionally substituted heteroaryl selected from the group consisting of an optionally substituted pyridinyl, an optionally substituted thienyl, an optionally substituted pyrrolyl, an optionally substituted oxazolyl, an optionally substituted imidazolyl, an optionally substituted indolizinyl, an optionally substituted isoxazolyl, an optionally substituted pyrazolyl, an optionally substituted isothiazolyl, an optionally substituted pyridazinyl, an optionally substituted pyrimidinyl, an optionally substituted pyrazinyl, an optionally substituted triazinyl, an optionally substituted triazolyl, an optionally substituted pyridinyl, an optionally substituted thiadiazolyl, an optionally substituted pyrazinyl, an optionally substituted quinolinyl, an optionally substituted isoquniolinyl, an optionally substituted indazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzofuryl, an optionally substituted benzothiazolyl, an optionally substituted indolizinyl, an optionally substituted imidazopyridinyl, an optionally substituted tetrazolyl, an optionally substituted benzimidazolyl, an optionally substituted benzoxazolyl, an optionally substituted benzothiazolyl, an optionally substituted benzothiadiazolyl, an optionally substituted benzoxadiazolyl, an optionally substituted indolyl, an optionally substituted tetrahydroindolyl, an optionally substituted azaindolyl, an optionally substituted imidazopyridyl, an optionally substituted qunizaolinyl, an optionally substituted purinyl, an optionally substituted pyrrolo[2,3]pyrimidyl, an optionally substituted pyrazolo[3,4]pyrimidyl or an optionally substituted benzo(b)thienyl; or R 9  and R 10  taken together with the nitrogen to which they are attached are an optionally substituted heterocyclyl or optionally substituted heteroaryl;  
       q, for each occurrence, is independently, an integer from 1 to 3;  
       k is for each occurrence, is independently, an integer from 1 to 4;  
       n is zero, 1 or 2; and  
       p, for each occurrence, is independently 1 or 2.  
     
   
   
       81 . The method of  claim 80 , wherein the subject is human.  
   
   
       82 . The method of  claim 80 , wherein the disorder is allergic rhinitis, sinusitis, rhinosinusitis, chronic otitis media, recurrent otitis media, drug reactions, insect sting reactions, latex reactions, conjunctivitis, urticaria, anaphylaxis reactions, anaphylactoid reactions, atopic dermatitis, asthma, or food allergies.