Compositions for treating epithelial and retinal tissue diseases

A compound of Formula I, or a pharmaceutically acceptable salt thereof:

• wherein
• A is a covalently bound substituent having a maximum molecular weight of 1000 and is OR1 or SR1, wherein R1 is cycloalkyl without substituents, aryl, arylalkyl, phosphonate, or acylthioalkyl with or without substituents or heteroatoms;
• X1, X2, and X3 are independently oxygen, methylene, monochloromethylene, dichloromethylene, monofluoromethylene, difluoromethylene, or imido;
• T1, T2, W, and V are independently oxygen or sulfur;
• m=0, 1, or 2;
• n=0 or 1;
• p=0, 1, or 2;
• where the sum of m+n+p is from 0 to 5;
• M=H or a pharmaceutically-acceptable inorganic or organic counter ion;
• D=O or CH2;
• B is a purine or a pyrimidine residue according to general Formulae IV and V which is linked to the 1′ position of the furanose or carbocycle via the 9- or 1- position of the base, respectively;
• Y=H, OH, or OR4;
• Z=H, OH, or OR5;
• with the proviso that Y and Z are both not H;
• R4 and R5 are residues which are linked directly to the 2′ and/or 3′ oxygens of the furanose or carbocycle via a carbon atom according to Formula II, or linked directly to the two 2′ and 3′ oxygens of the furanose or carbocycle via a common carbon atom according to Formula III;
• wherein:
• O is the corresponding 2′ and/or 3′ oxygen of the furanose or carbocycle;
• C is the carbon atom;
• R6, R7, and R8 are H, an alkyl, cycloalkyl, aralkyl, aryl, substituted aralkyl, or substituted aryl, such that the moiety defined according to Formula II is an ether;
• or
• R6 and R7 are H, an alkyl, cycloalkyl, aralkyl, aryl, substituted aralkyl, or substituted aryl, and R8 is alkoxy, cycloalkoxy, aralkyloxy, aryloxy, substituted aralkyloxy, or substituted aryloxy such that the moiety defined according to formula II is an acyclic acetal or ketal;
• or
• R6 and R7 are taken together as oxygen or sulfur doubly bonded to C, and R8 is alkyl, cycloalkyl, aralkyl, aryl, substituted aralkyl, or substituted aryl, such that the moiety defined according to Formula II is an ester or thioester;
• or
• R6 and R7 are taken together as oxygen or sulfur doubly bonded to C, and R8 is amino or mono- or disubstituted amino, where the substituents are alkyl, cycloalkyl, aralkyl, aryl, substituted aralkyl, or substituted aryl, such that the moiety according to Formula II is a carbamate or thiocarbamate;
• or
• R6 and R7 are taken together as oxygen or sulfur doubly bonded to C, and R8 is alkoxy, cycloalkoxy, aralkyloxy, aryloxy, substituted aralkyloxy, or substituted aryloxy, such that the moiety according to Formula H is a carbonate or thiocarbonate;
• or
• R8 is not present and R6 and R7 are taken together as oxygen or sulfur doubly bonded to C and both the 2′ and 3′ oxygens of the furanose are directly bound to C to form a cyclical carbonate or thiocarbonate;
• wherein:
• O is the 2′ and 3′ oxygens of the furanose or carbocycle;
• and the 2′ and 3′ oxygens of the furanose or carbocycle are linked by a common carbon atom to form a cyclical acetal, cyclical ketal, or cyclical orthoester;
• for cyclical acetals and ketals, R9 and R10 are independently hydrogen, alkyl, cycloalkyl, aralkyl, aryl, substituted aralkyl, substituted aryl, or can be joined together to form a homocyclic or heterocyclic ring composed of 3 to 8 atoms;
• for cyclical orthoesters, R9 is hydrogen, alkyl, cycloalkyl, aralkyl, aryl, substituted aralkyl, or substituted aryl, R10 is alkyloxy, cycloalkyloxy, aralkyloxy, aryloxy, substituted aralkyloxy, or substituted aryloxy;
• wherein:
• R11 and R15 are hydroxy, oxo, amino, mercapto, alkylthio, alkyloxy, aryloxy, alkylamino, cycloalkylamino, aralkylamino, arylamino, diaralkylamino, diarylamino, or dialkylamino, where the alkyl groups are optionally linked to form a heterocycle;
• or
• R11 and R15 are acylamino;
• or
• when R11 in a purine or R15 in a pyrimidine has as its first atom nitrogen, R11 and R12 or R15 and
• R16 are taken together to form a 5-membered fused imidazole ring optionally substituted on the etheno ring with alkyl, cycloalkyl, aralkyl, or aryl moieties;
• when R15 in a pyrimidine has as its first atom oxygen, R15 and R17 are taken together to form a 5-membered dihydrofuran ring, optionally substituted on the dihydrofuran ring with alkyl, cycloalkyl, aralkyl, or aryl moieties;
• J is carbon or nitrogen, with the provision that when nitrogen, R13 is not present;
• R12 is hydrogen, O or is absent;
• R16 is hydrogen, or acyl;
• R13 is hydrogen, alkyl, bromo, azido, alkylamino, arylamino or aralkylamino, alkoxy, aryloxy or aralkyloxy, alkylthio, arythio or aralkylthio, or ω-E(C1-6alkyl)G-, wherein E and G are independently amino, mercapto, hydroxy or carboxyl;
• R14 is hydrogen, chlorine, amino, monosubstituted amino, disubstituted amino, alkylthio, arylthio, or aralkylthio, where the substituent on sulfur contains up to a maximum of 20 carbon atoms, with or without unsaturation;
• and
• R17 is hydrogen, methyl, alkyl, halo, alkyl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl.