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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 forma

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.

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1. A compound of formula (I): 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 CRX, wherein RX is hydrogen; halogen; substituted or unsubstituted

1. A compound of formula (I): 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 CRX, wherein RX is hydrogen; halogen; substituted or unsubstituted aliphatic; substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —ORF; —SRF; —N(RF)2; and —C(RF)3; wherein each occurrence of RF 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, NRY, C or CRY, wherein each occurrence of RY is independently hydrogen; halogen; substituted or unsubstituted heteroaryl; —ORG; —C(═O)RG; —CO2RG; —C(═O)N(RG)2; —CN; —SCN; —SRG; —SORG; —SO2RG; —NO2; —N(RG)2; or —NHC(O)RG; wherein each occurrence of RG 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, wherein one, two, or three occurrences of Y are CH;each occurrence of T and G is independently —S—, —O—, —NRE—, or —C(RE)2—, wherein each occurrence of RE is independently hydrogen; halogen; substituted or unsubstituted aliphatic; substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —ORG; —SRG; —N(RG)2; and —C(RG)3; wherein each occurrence of RG 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;R1 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 aryl; substituted or unsubstituted heteroaryl; —C(═O)RA; —C(═O)ORA; —C(═O)N(RA)2; or —C(RA)3; wherein each occurrence of RA 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 R2 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 aryl; substituted or unsubstituted heteroaryl; —ORB; —C(═O)RB; —CO2RB; —C(═O)N(RB)2; —CN; —SCN; —SRB; —SORB; —SO2RB; —NO2; —N(RB)2; —NHC(O)RB; or —C(RB)3; wherein each occurrence of RB 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;R3 is halogen; —OH; or —CO2RC; wherein each occurrence of RC is independently a hydrogen; a protecting group; an aliphatic moiety; a heteroaliphatic moiety; an acyl moiety; an aryl moiety; or a heteroaryl moiety;R4 and R5 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 aryl; substituted or unsubstituted heteroaryl; —ORD; —C(═O)RD; —CO2RD; —C(═O)N(RD)2; —CN; —SCN; —SRD; —SORD; —SO2RD; —NO2; —N(RD)2; —NHC(O)RD; or —C(RD)3; wherein each occurrence of RD 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; andR6 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —ORK; —C(═O)RK; —CO2RK; —C(═O)N(RK)2; —CN; —SCN; —SRK; —SORK; —SO2RK; —NO2; —N(RK)2; —NHC(O)RK; or —C(RK)3; wherein each occurrence of RK 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;and pharmaceutically acceptable salts thereof. 2. The compound of claim 1 of formula: 3. The compound of claim 1, wherein R6 is hydrogen. 4. The compound of claim 1 of formula: 5. A compound of formula (VI): wherein j is an integer between 1 and 8, inclusive;each occurrence of Y is S, O, N, or CRY, wherein each occurrence of RY is independently 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 aryl; substituted or unsubstituted heteroaryl; —ORG; —C(═O)RG; —CO2RG; —C(═O)N(RG)2; —CN; —SCN; —SRG; —SORG; —SO2RG; —NO2; —N(RG)2; —NHC(O)RG; or —C(RG)3; wherein each occurrence of RG 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;Z is ═O or ═N—NHRD, wherein RD is 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;R1 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 aryl; substituted or unsubstituted heteroaryl; —C(═O)RA; —C(═O)ORA; —C(═O)N(RA)2; or —C(RA)3; wherein each occurrence of RA 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 R2 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 aryl; substituted or unsubstituted heteroaryl; —ORB; —C(═O)RB; —CO2RB; —C(═O)N(RB)2; —CN; —SCN; —SRB; —SORB; —SO2RB; —NO2; —N(RB)2; —NHC(O)RB; or —C(RB)3; wherein each occurrence of RB 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;R3 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 aryl; substituted or unsubstituted heteroaryl; —ORC; —C(═O)RC; —CO2RC; —C(═O)N(RC)2; —CN; —SCN; —SRC; —SORC; —SO2RC; —NO2; —N(RC)2; —NHC(O)RC; or —C(RC)3; wherein each occurrence of RC 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; andR6 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 aryl; substituted or unsubstituted heteroaryl; —ORK; —C(═O)RK; —CO2RK; —C(═O)N(RK)2; —CN; —SCN; —SRK; —SORK; —SO2RK; —NO2; —N(RK)2; —NHC(O)RK; or —C(RK)3; wherein each occurrence of RK 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; and pharmaceutically acceptable salts thereof;provided that at least one instance of Y is not CRY. 6. The compound of claim 5 of formula: 7. The compound of claim 5 of formula: 8. A compound of formula (XI): wherein represents a double or triple bond;n is an integer between 0 and 3, inclusive;j is an integer between 0 and 8, inclusive;R1 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 aryl; substituted or unsubstituted heteroaryl; —C(═O)RA; —C(═O)ORA; —C(═O)N(RA)2; or —C(RA)3; wherein each occurrence of RA 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 RY 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 aryl; substituted or unsubstituted heteroaryl; —ORG; —C(═O)RG; —CO2RG; —C(═O)N(RG)2; —CN; —SCN; —SRG; —SORG; —SO2RG; —NO2; —N(RG)2; —NHC(O)RG; or —C(RG)3; wherein each occurrence of RG 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 R2 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 aryl; substituted or unsubstituted heteroaryl; —ORB; —C(═O)RB; —CO2RB; —C(═O)N(RB)2; —CN; —SCN; —SRB; —SORB; —SO2RB; —NO2; —N(RB)2; —NHC(O)RB; or —C(RB)3; wherein each occurrence of RB 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;R3 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 aryl; substituted or unsubstituted heteroaryl; —ORC; —C(═O)RC; —CO2RC; —C(═O)N(RC)2; —CN; —SCN; —SRC; —SORC; —SO2RC; —NO2; —N(RC)2; —NHC(O)RC; or —C(RC)3; wherein each occurrence of RC 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;R6 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 aryl; substituted or unsubstituted heteroaryl; —ORK; —C(═O)RK; —CO2RK; —C(═O)N(RK)2; —CN; —SCN; —SRK; —SORK; —SO2RK; —NO2; —N(RK)2; —NHC(O)RK; or —C(RK)3; wherein each occurrence of RK 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; andR7 is hydrogen; halogen; cyclic or acyclic, unsubstituted, branched or unbranched alkyl; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkenyl; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkynyl; cyclic or acyclic, substituted or unsubstituted, branched or unbranched carbocyclyl; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —ORC; —C(═O)RC; —CO2RC; —C(═O)N(RC)2; —CN; —SCN; —SRC; —SORC; —SO2RC; —NO2; —N(RC)2; —NHC(O)RC; —Si(RC)3; or —C(RC)3; wherein each occurrence of RC 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; and pharmaceutically acceptable salts thereof. 9. A compound of Formula (XIII): wherein j is an integer between 0 and 6, inclusive;each occurrence of Y is independently S, O, N, C or CRY, wherein each occurrence of RY 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 aryl; substituted or unsubstituted heteroaryl; —ORG; —C(═O)RG; —CO2RG; —C(═O)N(RG)2; —CN; —SCN; —SRG; —SORG; —SO2RG; —NO2; —N(RG)2; —NHC(O)RG; or —C(RG)3; wherein each occurrence of RG 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, wherein one, two, or three occurrences of Y are CH;R1 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 aryl; substituted or unsubstituted heteroaryl; —C(═O)RA; —C(═O)ORA; —C(═O)N(RA)2; or —C(RA)3; wherein each occurrence of RA 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; provided that R1 is not a tert-butoxycarbonyl group;each occurrence of R2 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 aryl; substituted or unsubstituted heteroaryl; —ORB; —C(═O)RB; —CO2RB; —C(═O)N(RB)2; —CN; —SCN; —SRB; —SORB; —SO2RB; —NO2; —N(RB)2; —NHC(O)RB; or —C(RB)3; wherein each occurrence of RB 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;R3 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 aryl; substituted or unsubstituted heteroaryl; —ORC; —C(═O)RC; —CO2RC; —C(═O)N(RC)2; —CN; —SCN; —SRC; —SORC; —SO2RC; —NO2; —N(RC)2; —NHC(O)RC; or —C(RC)3; wherein each occurrence of RC 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; provided that R3 is not —OCH2Ph;R4 and R5 are independently hydrogen or —OH; andR6 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —ORK; —C(═O)RK; —CO2RK; —C(═O)N(RK)2; —CN; —SCN; —SRK; —SORK; —SO2RK; —NO2; —N(RK)2; —NHC(O)RK; or —C(RK)3; wherein each occurrence of RK 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; and pharmaceutically acceptable salts thereof. 10. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient or vehicle. 11. The compound of claim 1, wherein X is N. 12. The compound of claim 11, wherein T is —C(RE)2—. 13. The compound of claim 12, wherein G is —C(RE)2—. 14. The compound of claim 13, wherein p is 1. 15. The compound of claim 14, wherein q is 1. 16. The compound of claim 1, wherein RC is hydrogen. 17. The compound of claim 1, wherein one occurrence of Y is CH. 18. The compound of claim 1, wherein two occurrences of Y are CH. 19. The compound of claim 1, wherein three occurrences of Y are CH. 20. The compound of claim 1, wherein m is 1 and v is 1 or 2. 21. The compound of claim 1, wherein m is 2 and v is 1 or 2. 22. The compound of claim 5, wherein R6 is hydrogen. 23. The compound of claim 22 of formula: 24. The compound of claim 22 of formula: 25. The compound of claim 22 of formula: 26. The compound of claim 22 of formula: 27. The compound of claim 8, wherein R6 is hydrogen. 28. The compound of claim 27, wherein the compound is one of the following: 29. A compound selected from the group consisting of: