Halofuginone analogs for inhibition of trna synthetases and uses thereof

Abstract

The present invention provides novel analogs and derivatives of halofuginone. The invention also provides pharmaceutical and cosmetic compositions thereof and methods for using halofuginone analogs in treating chronic inflammatory diseases, autoimmune diseases, dry eye syndrome, fibrosis, scar formation, angiogenesis, viral infections, ischemic damage, transplant and implant rejection, neurodegenerative diseases, and cosmetic applications.

1 - 172 . (canceled) 
     
     
         173 . A method of inhibiting glutamyl-prolyl tRNA synthetase comprising contacting glutamyl-prolyl tRNA synthetase with a compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, 
         wherein:
 j is an integer between 0 and 10, inclusive; 
 p is an integer between 0 and 6, inclusive; 
 q is an integer between 0 and 6, inclusive; 
 m is 1 or 2; 
 v is an integer between 1 and 3, inclusive; 
 X is N or CR X , wherein R X  is hydrogen halogen; substituted or unsubstituted aliphatic substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR F ; −SR F ; —N(R F ) 2 ; and —C(R F ) 3 ; wherein each occurrence of R F  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of Y is independently S, O, N, NR Y , or CR Y , wherein each occurrence of R Y  is independently hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR G ; —C(═O)R G ; —CO 2 R G ; —C(═O)N(R G ) 2 ; —CN; —SCN; —SR G ; —SOR G ; —SO 2 R G ; —NO 2 ; —N(R G ) 2 ; —NHC(O)R G ; or —C(R G ) 3 ; wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of T and G is independently —S—, —O—, —NR E —, or C(R E ) 2 —, wherein each occurrence of R E  is independently hydrogen; halogen; substituted or unsubstituted aliphatic substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR G ; —SR G ; —N(R G ) 2 ; and —C(R G ) 3 ; wherein each occurrence of R G , is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 1  is hydrogen; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —C(═O)R A ; —C(═O)OR A ; —C(═O)N(R A ) 2 ; or —C(R A ) 3  wherein each occurrence of R A  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of R 2  is independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR B ; —C(═O)R B ; —CO 2 R B ; —C(═O)N(R B ) 2 ; —CN; —SCN; —SR B ; —SOR B ; —SO 2 R B ; —NO 2 ; —N(R B ) 2 ; —NHC(O)R B ; or —C(R B ) 3 ; wherein each occurrence of R B  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 3  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR C ; —C(═O)R C ; —CO 2 R C ; —C(═O)N(R C ); —CN; —SCN; —SR C ; —SOR C ; —SO 2 R C ; —NO 2 ; —N(R C ) 2 ; —NHC(O)R C ; or —C(R C ) 3 ; wherein each occurrence of R C  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 4  and R 5  are independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl: substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR D ; —C(═O)R D ; —CO 2 R D ; —C(═O)N(R D ) 2 ; —CN; —SCN; —SR D ; —SOR D ; —SO 2 R D ; —NO 2 ; —N(R D ) 2 ; —NHC(O)R D ; or —C(R D ) 3 ; wherein each occurrence of RR is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; or 
 R 4  and R 5  may optionally be taken together to form ═O, ═S, ═NR D , ═N—OR D , ═N—NHR D , ═N—N(R D ) 2 , ═C(R D ) 2 ; or 
 R 4  and R 5  may optionally be taken together with the intervening atom to form a saturated or unsaturated, substituted or unsubstituted cyclic or heterocyclic structure; and 
 R 6  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR K ; —C(═O)R K ; —CO 2 R K ; —C(═O)N(R K ) 2 ; —CN; —SCN; —SR K ; —SOR K ; —SO 2 R K ; —NO 2 ; —N(R K ) 2 ; —NHC(O)R K ; or —C(R K ) 3 ; wherein each occurrence of R K  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety, a heteroaryl moiety, alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety. 
 
       
     
     
         174 . The method of  claim 173 , wherein the glutamyl-prolyl tRNA synthetase is contacted in vitro. 
     
     
         175 . The method of  claim 174 , wherein the glutamyl-prolyl tRNA synthetase is purified. 
     
     
         176 . The method of  claim 173 , wherein the glutamyl-prolyl tRNA synthetase in contacted in a cell. 
     
     
         177 . A method of treating a Th17-mediated condition comprising administering to a subject a compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, 
         wherein:
 j is an integer between 0 and 10, inclusive; 
 p is an integer between 0 and 6, inclusive; 
 q is an integer between 0 and 6, inclusive; 
 m is 1 or 2; 
 v is an integer between 1 and 3, inclusive; 
 X is N or CR X , wherein R X  is hydrogen, halogen; substituted or unsubstituted aliphatic; substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR F ; —SR F ; —N(R F ) 2 ; and —C(R F ) 3 ; wherein each occurrence of R F  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of Y is independently S, O, N, NR Y , or CR Y , wherein each occurrence of R Y  is independently hydrogen; halogen, cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic, cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR G ; —C(═O)R G ; —CO 2 R G ; —C(═O)N(R G ) 2 ; —CN; —SCN; —SR G ; —SOR G ; —SO 2 R G ; —NO 2 ; —N(R G ) 2 ; —NHC(O)R G ; or —C(R G ) 3 ; wherein each occurrence of R C  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of T and G is independently —S—, —O—, —NR E —, or C(R E ) 2 —, wherein each occurrence of R E  is independently hydrogen; halogen, substituted or unsubstituted aliphatic; substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR; —SR G ; —N(R G ) 2 ; and —C(R G ) 3 ; wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 1  is hydrogen a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —C(═O)R A ; —C(═O)OR A ; —C(═O)N(R A ) 2 ; or —C(R A ) 3  wherein each occurrence of R A  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of R 2  is independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR B ; —C(═O)R B ; —CO 2 R B ; —C(═O)N(R B ) 2 ; —CN; —SCN; —SR B ; —SOR B ; —SO 2 R B ; —NO 2 ; —N(R B ) 2 ; —NHC(O)R B ; or —C(RB) 2 ; wherein each occurrence of R B  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 3  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR C ; —C(═O)R C ; —CO 2 R C ; —C(═O)N(R C ) 2 ; —CN; —SCN; —SR C ; —SOR C ; —SO 2 R C ; —NO 2 ; —N(R C ) 2 ; —NHC(O)R C ; or —C(R C ) 3 ; wherein each occurrence of R C  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 4  and R 5  are independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR D ; —C(═O)R D ; —CO 2 R D ; —C(═O)N(R D ) 2 ; —CN; —SCN; —SR D ; —SOR D ; —SO 2 R D ; —NO 2 ; —N(R D ) 2 ; —NHC(O)R D ; or —C(R D ) 3 ; wherein each occurrence of R D  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety, an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; or 
 R 4  and R 5  may optionally be taken together to form ═O, ═S, ═NR D , ═N—OR D , ═N—NHR D , ═N—N(R D ) 2 , ═C(R D ) 2 ; or 
 R 4  and R 5  may optionally be taken together with the intervening atom to form a saturated or unsaturated, substituted or unsubstituted cyclic or heterocyclic structure; and 
 R 6  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR K ; —C(═O)R K ; —CO 2 R K ; —C(═O)N(R K ) 2 ; —CN; —SCN; —SR K ; —SOR K ; —SO 2 R K ; —NO 2 ; —N(R K ) 2 ; —NHC(O)R K ; or —C(R K ) 3 ; wherein each occurrence of R K  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety. 
 
       
     
     
         178 . The method of  claim 177 , wherein the Th17-mediated condition is selected from the group consisting of autoimmune diseases, dry eye syndrome, fibrosis, scar formation, angiogenesis, ischemic damage, inflammatory diseases, and neurodegenerative diseases. 
     
     
         179 . The method of  claim 177 , wherein the Th17-mediated condition is selected from cellulite or stretch marks. 
     
     
         180 . The method of  claim 177  further comprising administering a second agent that inhibits expression or activity of a proinflammatory cytokine. 
     
     
         181 . The method of  claim 180 , wherein the proinflammatory cytokine is selected from one or more of TNFα, IFNγ, GM-CSF, MIP-2, IL-12, IL-1α, IL-I β, and IL-23. 
     
     
         182 - 183 . (canceled) 
     
     
         184 . The method of  claim 180 , wherein the proinflammatory cytokine is IL-6 or IL-21. 
     
     
         185 - 192 . (canceled) 
     
     
         193 . A method of treating a glutamyl-prolyl tRNA synthetase-mediated condition comprising administering to a subject a compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, 
         wherein:
 j is an integer between 0 and 10, inclusive; 
 p is an integer between 0 and 6, inclusive; 
 q is an integer between 0 and 6, inclusive; 
 m is 1 or 2; 
 v is an integer between 1 and 3, inclusive; 
 X is N or CR X , wherein R X  is hydrogen, halogen; substituted or unsubstituted aliphatic; substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR F ; —SR F ; —N(R F ) 2 ; and —C(R F ) 3 ; wherein each occurrence of R F  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of Y is independently S, O, N, NR Y , or CR Y , wherein each occurrence of R is independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR G ; —C(═O)R G ; —CO 2 R G ; —C(═O)N(R G ) 2 ; —CN; —SCN; —SR G ; —SOR G ; —SO 2 R G ; —NO 2 ; —N(R G ) 2 ; —NHC(O)R G ; or —C(R G ) 3 ; wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of T and G is independently —S—, —O—, —NR E —, or C(R E ) 2 —, wherein each occurrence of R E  is independently hydrogen; halogen; substituted or unsubstituted aliphatic substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR G ; —SR G ; —N(R G ) 2 ; and —C(R G ) 3 ; wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 1  is hydrogen a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —C(═O)R A ; —C(═O)OR A ; —C(═O)N(R A ) 2 ; or —C(R A ) 3 ; wherein each occurrence of R A  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of R 2  is independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR B ; —C(═O)R B ; —CO 2 R B ; —C(═O)N(R B ) 2 ; —CN; —SCN; —SR B ; —SOR B ; —SO 2 R B ; —NO 2 ; —N(R B ) 2 ; —NHC(O)R B ; or —C(R B ) 3 ; wherein each occurrence of R B  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 3  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR C ; —C(═O)R C ; —CO 2 R C ; —C(═O)N(R B ) 2 ; —CN; —SCN; —SR C ; —SOR C ; —SO 2 R C ; —NO 2 ; —N(R C ) 2 ; —NHC(O)R C ; or —C(R C ) 3 ; wherein each occurrence of RP is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 4  and R 5  are independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR D ; —C(═O)R D ; —CO 2 R D ; —C(═O)N(R D ) 2 ; —CN; —SCN; —SR D ; —SOR D ; —SO 2 R D ; —NO 2 ; —N(R D ) 2 ; —NHC(O)R D ; or —C(R D ) 3 ; wherein each occurrence of R D  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; or 
 R 4  and R 5  may optionally be taken together to form ═O, —S, ═NR D , ═N—OR D , ═N—NHR D , ═N—N(R D ) 2 , —C(R D ) 2 ; or 
 R 4  and R 5  may optionally be taken together with the intervening atom to form a saturated or unsaturated, substituted or unsubstituted cyclic or heterocyclic structure; and 
 R 6  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic, cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR K ; —C(═O)R K ; —CO 2 R K ; —C(═O)N(R K ) 2 ; —CN; —SCN; —SR; —SOR K ; —SO 2 R K ; —NO 2 ; —N(R K ) 2 ; —NHC(O)R K ; or —C(R K ) 3 , wherein each occurrence of R K  is independently a hydrogen, a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety, a heteroaryl moiety, alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety. 
 
       
     
     
         194 . The method of  claim 193 , wherein the glutamyl-prolyl tRNA synthetase-mediated condition involves collagen synthesis. 
     
     
         195 . A method of treating fibrosis comprising administering to a subject a compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, 
         wherein:
 j is an integer between 0 and 10, inclusive; 
 p is an integer between 0 and 6, inclusive; 
 q is an integer between 0 and 6, inclusive; 
 m is 1 or 2; 
 v is an integer between 1 and 3, inclusive; 
 X is N or CR X , wherein R X  is hydrogen halogen; substituted or unsubstituted aliphatic substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR F ; —SR F ; —N(R F ) 2 ; and —C(R F ) 3 ; wherein each occurrence of R F  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of Y is independently S, O, N, NR Y , or CR Y , wherein each occurrence of R Y  is independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR G ; —C(═O)R G ; —CO 2 R G ; —C(═O)N(R G ) 2 ; —CN; —SCN; —SR G ; —SOR G ; —SO 2 R G ; —NO 2 ; —N(R G ) 2 ; —NHC(O)R G ; or —C(R G ) 3 ; wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of T and G is independently —S—, —O—, —NR E —, or C(R E ) 2 —, wherein each occurrence of R E  is independently hydrogen; halogen; substituted or unsubstituted aliphatic substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR G ; —SR G ; —N(R G ) 2 ; and —C(R G ) 3 ; wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 1  is hydrogen a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —C(═O)R A ; —C(═O)OR A ; —C(═O)N(R A ) 2 ; or —C(R A ) 3 ; wherein each occurrence of R A  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of R, is independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR B ; —C(═O)R B ; —CO 2 R B ; —C(═O)N(R B ) 2 ; —CN; —SCN; —SR B ; —SOR B ; —SO 2 R B ; —NO 2 ; —N(R B ) 2 ; —NHC(O)R B ; or —C(R B ) 3 ; wherein each occurrence of R B  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 3  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR C ; —C(═O)R C ; —CO 2 R C ; —C(═O)N(R C ) 2 ; —CN; —SCN; —SR C ; —SOR C ; —SO 2 R C ; —NO 2 ; —N(R C ) 2 ; —NHC(O)R C ; or —C(R C ) 3 ; wherein each occurrence of R C  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 4  and R 5  are independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR D ; —C(═O)R D ; —CO 2 R D ; —C(═O)N(R D ) 2 ; —CN; —SCN; —SR D ; —SOR D ; —SO 2 R D ; —NO 2 ; —N(R D ) 2 ; —NHC(O)R D ; or —C(R D ) 3 ; wherein each occurrence of R D  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; or 
 R 4  and R 5  may optionally be taken together to form ═O, ═S, ═NR D , ═N—OR D , ═N—NHR D , ═N—N(R n ) 2 , ═C(R D ) 2 ; or 
 R 4  and R 5  may optionally be taken together with the intervening atom to form a saturated or unsaturated, substituted or unsubstituted cyclic or heterocyclic structure; and 
 R 6  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR K ; —C(═O)R K ; —CO 2 R K ; —C(═O)N(R K ) 2 ; —CN; —SCN; —SR K ; —SOR K ; —SO 2 R K ; —NO 2 ; —N(R K ) 2 ; —NHC(O)R K ; or —C(R K ) 3 ; wherein each occurrence of R K  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety. 
 
       
     
     
         196 . A method of protecting a donor organ for transplantation, comprising contacting said organ with a compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, 
         wherein:
 j is an integer between 0 and 10, inclusive; 
 p is an integer between 0 and 6, inclusive; 
 q is an integer between 0 and 6, inclusive; 
 m is 1 or 2; 
 v is an integer between 1 and 3, inclusive; 
 X is N or CR X , wherein R X  is hydrogen, halogen; substituted or unsubstituted aliphatic; substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR F ; —SR F ; —N(R F ) 2 ; and —C(R F ) 3 ; wherein each occurrence of R F  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of Y is independently S, O, N, NR Y , or CR Y , wherein each occurrence of R Y  is independently hydrogen; halogen, cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic, cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR G ; —C(═O)R G ; —CO 2 R G ; —C(═O)N(R G ) 2 ; —CN; —SCN; —SR G ; —SOR G ; —SO 2 R G ; —NO 2 ; —N(R G ) 2 ; —NHC(O)R G ; or —C(R G ) 3 ; wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of T and G is independently —S—, —O—, —NR E —, or C(R E ) 2 —, wherein each occurrence of R E  is independently hydrogen; halogen, substituted or unsubstituted aliphatic; substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR G ; —SR G ; —N(R G ) 2 ; and —C(R G ) 3 , wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 1  is hydrogen; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic, cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —C(═O)R A ; —C(═O)OR A ; —C(═O)N(R A ) 2 ; or —C(R A ) 3  wherein each occurrence of R A  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of R 2  is independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR B ; —C(═O)R B ; —CO 2 R B ; —C(═O)N(R B ) 2 ; —CN; —SCN; —SR B ; —SOR B ; —SOR 2 R B ; —NO 2 ; —N(R B ) 2 ; —NHC(O)R B ; or —C(R B ) 3 ; wherein each occurrence of R B  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 3  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR C ; —C(═O)R C ; —CO 2 R C ; —C(═O)N(R C ) 2 ; —CN; —SCN; —SR C ; —SOR C ; —SO 2 R C ; —NO 2 ; —N(R C ) 2 ; —NHC(O)R C ; or —C(R C ) 3 ; wherein each occurrence of R C  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 4  and R 5  are independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR D ; —C(═O)R D ; —CO 2 R D ; —C(═O)N(R D ) 2 ; —CN; —SCN; —SR D ; —SOR D ; —SO 2 R D ; —NO 2 ; —N(R D ) 2 ; —NHC(O)R D ; or —C(R D ) 3 ); wherein each occurrence of R D  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; or 
 R 4  and R 5  may optionally be taken together to form ═O, ═S, ═NR D , ═N—OR D , ═N—NHR D , ═N—N(R D ) 2 , ═C(R D ) 2 ; or 
 R 4  and R 5  may optionally be taken together with the intervening atom to form a saturated or unsaturated, substituted or unsubstituted cyclic or heterocyclic structure; and 
 R 6  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR K ; —C(═O)R K ; —CO 2 R K ; —C(═O)N(R_); —CN; —SCN; —SR K ; —SOR K ; —SO 2 R K ; —NO 2 ; —N(R K ) 2 ; —NHC(O)R K ; or —C(R K ) 3 ; wherein each occurrence of R K  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety. 
 
       
     
     
         197 . A method of treating an AAR-mediated condition comprising administering to a subject a compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, 
         wherein:
 j is an integer between 0 and 10, inclusive; 
 p is an integer between 0 and 6, inclusive; 
 q is an integer between 0 and 6, inclusive; 
 m is 1 or 2; 
 v is an integer between 1 and 3, inclusive; 
 X is N or CR X , wherein R X  is hydrogen halogen; substituted or unsubstituted aliphatic substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR F ; —SR F ; —N(R F ) 2 ; and —C(R F ) 3 ; wherein each occurrence of R F  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of Y is independently S, O, N, NR Y , or CR Y , wherein each occurrence of R Y  is independently hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR G ; —C(═O)R G ; —CO 2 R G ; —C(═O)N(R G ) 2 ; —CN; —SCN; —SR G ; —SOR G ; —SO 2 R G ; —NO 2 ; —N(R G ) 2 ; —NHC(O)R G ; or —C(R G ) 3 ; wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 
         each occurrence of T and G is independently —S—, —O—, —NR E —, or C(R E ) 2 —, wherein each occurrence of R E  is independently hydrogen; halogen; substituted or unsubstituted aliphatic substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR G ; —SR G ; —N(R G ) 2 ; and —C(R G ) 3 ; wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety;
 R 1  is hydrogen; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —C(═O)R A ; —C(═O)OR A ; —C(═O)N(R A ) 2 ; or —C(R A ) 3  wherein each occurrence of R A  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of R 2  is independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR B ; —C(═O)R B ; —CO 2 R B ; —C(═O)N(R B ) 2 ; —CN; —SCN; —SR B ; —SOR B ; —SOR 2 R B ; —NO 2 ; —N(R B ) 2 ; —NHC(O)R B ; or —C(R B ) 3 ; wherein each occurrence of R B  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 3  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR C ; —C(═O)R C ; —CO 2 R C ; —C(═O)N(R C ) 2 ; —CN; —SCN; —SR C ; —SOR C ; —SO 2 R C ; —NO 2 ; —N(R C ) 2 ; —NHC(O)R C ; or —C(R C ) 3 ; wherein each occurrence of R C  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 4  and R 5  are independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR D ; —C(═O)R D ; —CO 2 R D ; —C(═O)N(R D ) 2 ; —CN; —SCN; —SR D ; —SOR D ; —SO 2 R D ; —NO 2 ; —N(R D ) 2 ; —NHC(O)R D ; or —C(R D ) 3 ); wherein each occurrence of R D  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; or 
 R 4  and R 5  may optionally be taken together to form ═O, ═S, ═NR D , ═N—OR D , ═N—NHR D , ═N—N(R D ) 2 , —C(R D ) 2 ; or 
 R 4  and R 5  may optionally be taken together with the intervening atom to form a saturated or unsaturated, substituted or unsubstituted cyclic or heterocyclic structure; and 
 R 6  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR K ; —C(═O)R K ; —CO 2 R K ; —C(═O)N(R K ) 2 ; —CN; —SCN; —SR K ; —SOR K ; —SO 2 R K ; —NO 2 ; —N(R K ) 2 ; —NHC(O)R K ; or —C(R K ) 3 ; wherein each occurrence of R K  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety. 
 
       
     
     
         198 . The method of  claim 197 , wherein the AAR-mediated condition is selected from the group consisting of fibrosis, scar formation, autoimmune disease, dry eye syndrome, graft versus host disease, angiogenesis, cancer, macular degeneration, choroidal neovascularization, asthma, chronic inflammation, cardiovascular disease, diabetes, viral infection, protozol infection, fungal infection, cellulite, and stretch marks. 
     
     
         199 . The method of  claim 198 , wherein the autoimmune disease is selected from multiple sclerosis, rheumatoid arthritis, lupus, psoriasis, scleroderma, or dry eye syndrome. 
     
     
         200 . (canceled) 
     
     
         201 . A method of treating cellulite comprising administering to a subject a compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, 
         wherein:
 j is an integer between 0 and 10, inclusive; 
 p is an integer between 0 and 6, inclusive; 
 q is an integer between 0 and 6, inclusive; 
 m is 1 or 2; 
 v is an integer between 1 and 3, inclusive; 
 X is N or CR X , wherein R X  is hydrogen halogen; substituted or unsubstituted aliphatic substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR F ; —SR F ; —N(R F ) 2 ; and —C(R F ) 3 ; wherein each occurrence of R F  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of Y is independently S, O, N, NR Y , or CR Y , wherein each occurrence of R Y  is independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR G ; —C(═O)R G ; —CO 2 R G ; —C(═O)N(R G ) 2 ; —CN; —SCN; —SR G ; —SOR G ; —SO 2 R G ; —NO 2 ; —N(R G ) 2 ; —NHC(O)R G ; or —C(R G ) 3 ; wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of T and G is independently —S—, —O—, —NR E —, or C(R E ) 2 —, wherein each occurrence of R E  is independently hydrogen; halogen; substituted or unsubstituted aliphatic substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR G ; —SR G ; —N(R G ) 2 ; and —C(R G ) 3 ; wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 1  is hydrogen a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —C(═O)R A ; —C(═O)OR A ; —C(═O)N(R A ) 2 ; or —C(R A ) 3 ; wherein each occurrence of R A  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of R 2  is independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR B ; —C(═O)R B ; —CO 2 R B ; —C(═O)N(R B ) 2 ; —CN; —SCN; —SR B ; —SOR B ; —SO 2 R B ; —NO 2 ; —N(R B ) 2 ; —NHC(O)R B ; or —C(R B ) 3 ; wherein each occurrence of R B  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 3  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR C ; —C(═O)R C ; —CO 2 R C ; —C(═O)N(R C ) 2 ; —CN; —SCN; —SR C ; —SOR C ; —SO 2 R C ; —NO 2 ; —N(R C ) 2 ; —NHC(O)R C ; or —C(R C ) 3 ; wherein each occurrence of R C  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 4  and R 5  are independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR D ; —C(═O)R D ; —CO 2 R D ; —C(═O)N(R D ) 2 ; —CN; —SCN; —SR D ; —SOR D ; —SO 2 R D ; —NO 2 ; —N(R D ) 2 ; —NHC(O)R D ; or —C(R D ) 3 ); wherein each occurrence of R D  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; or 
 R 4  and R 5  may optionally be taken together to form ═O, ═S, ═NR D , ═N—OR D , ═N—NHR D , ═N—N(R D ) 2 , ═C(R D ) 2 ; or 
 R 4  and R 5  may optionally be taken together with the intervening atom to form a saturated or unsaturated, substituted or unsubstituted cyclic or heterocyclic structure; and 
 R 6  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR K ; —C(═O)R K ; —CO 2 R K ; —C(═O)N(R K ) 2 ; —CN; —SCN; —SR K ; —SOR K ; —SO 2 R K ; —NO 2 ; —N(R K ) 2 ; —NHC(O)R K ; or —C(R K ) 3 ; wherein each occurrence of R K  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety. 
 
       
     
     
         202 . A method of treating a protozoal disease comprising administering to a subject a compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, 
         wherein:
 j is an integer between 0 and 10, inclusive; 
 p is an integer between 0 and 6, inclusive; 
 q is an integer between 0 and 6, inclusive; 
 m is 1 or 2; 
 v is an integer between 1 and 3, inclusive; 
 X is N or CR X , wherein R X  is hydrogen halogen; substituted or unsubstituted aliphatic substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR F ; —SR F ; —N(R F ) 2 ; and —C(R F ) 3 ; wherein each occurrence of R F  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of Y is independently S, O, N, NR Y , or CR Y , wherein each occurrence of R Y  is independently hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR; —C(═O)R G ; —CO 2 R G ; —C(═O)N(R G ) 2 ; —CN; —SCN; —SR G ; —SOR G ; —SO 2 R G ; —NO 2 ; —N(R G ) 2 ; —NHC(O)R G ; or —C(R G ) 3 , wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of T and G is independently —S—, —O—, —NR E —, or C(R E ) 2 —, wherein each occurrence of R E  is independently hydrogen; halogen; substituted or unsubstituted aliphatic substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR G ; —SR G ; —N(R G ) 2 ; and —C(R G ) 3 ; wherein each occurrence of R G  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 1  is hydrogen; a protecting group; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —C(═O)R A ; —C(═O)OR A ; —C(═O)N(R A ); or —C(R A ) 3  wherein each occurrence of R A  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 each occurrence of R 2  is independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR B ; —C(═O)R B ; —CO 2 R B ; —C(═O)N(R B ) 2 ; —CN; —SCN; —SR B ; —SOR B ; —SO 2 R B ; —NO 2 ; —N(R B ) 2 ; —NHC(O)R B ; or —C(R B ) 3 ; wherein each occurrence of R B  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 3  is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR C ; —C(═O)R C ; —CO 2 R C ; —C(═O)N(R C ) 2 ; —CN; —SCN; —SR C ; —SOR C ; —SO 2 R C ; —NO 2 ; —N(R C ) 2 ; —NHC(O)R C ; or —C(R C ) 3 ; wherein each occurrence of R C  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; 
 R 4  and R 5  are independently hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR D ; —C(═O)R D ; —CO 2 R D ; —C(═O)N(R D ) 2 ; —CN; —SCN; —SR D ; —SOR D ; —SO 2 R D ; —NO 2 ; —N(R D ) 2 ; —NHC(O)R D ; or —C(R D ) 3 ; wherein each occurrence of R D  is independently a hydrogen; a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety; or 
 R 4  and R 5  may optionally be taken together to form ═O, ═S, ═NR D , ═N—OR D , ═N—NHR D , ═N—N(R D ) 2 , —C(R D ) 2 ; or 
 R 4  and R 5  may optionally be taken together with the intervening atom to form a saturated or unsaturated, substituted or unsubstituted cyclic or heterocyclic structure; and 
 R 6  is hydrogen halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —OR K ; —C(═O)R K ; —CO 2 R K ; —C(═O)N(R K ) 2 ; —CN; —SCN; —SR K ; —SOR K ; —SO 2 R K ; —NO 2 ; —N(R K ) 2 ; —NHC(O)R K ; or —C(R K ) 3 ; wherein each occurrence of R K  is independently a hydrogen a halogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy moiety. 
 
       
     
     
         203 . The method of  claim 178 , wherein the disease is a neurodegenerative disease. 
     
     
         204 . The method of  claim 203 , wherein the disease is multiple sclerosis.