Adenosine Analogs and Their Use

A compound of formula IIA:

• including enantiomers, diastereomers, enantiomerically enriched mixtures, racemic mixtures, prodrugs, crystalline forms, non-crystalline forms, amorphous forms, solvates, metabolites, and pharmaceutically acceptable salts thereof, wherein:
• A, D, and E are independently N, C(R5), or CH;
• F is N or C(R4);
• R1 is H, oxo, lower alkoxy, lower alkylamino, lower dialkylamino, imino, lower alkyl-substituted imino, lower thioalkyl, aryl, substituted or unsubstituted lower alkyl, or lower alkyl-substituted aryl;
• R2 is absent or is selected from the group consisting of lower alkyl, lower alkoxy, lower alkyl-substituted aryl, aralkyl, and cycloalkyl;
• R3 and R4 are independently H, lower thioalkyl, substituted lower alkyl, or unsubstituted lower alkyl;
• R5 is lower alkyl, lower alkoxy, lower alkyl-substituted aryl, aralkyl, or cycloalkyl;
• Ar is aryl, alkyl, cycloalkyl, arylalkyl, or a heteroaryl or fused heteroaryl group containing 1-4 heteroatoms;
• each of which is optionally substituted with one or more of halo, hydroxy, alkyl, alkoxy, carboxy, cyano, nitro, sulfonamido, sulfonate, amino, alkylamino, or di-alkylamino;
• provided that when X is O, Ar is neither unsubstituted phenyl, anilino, nor 4-nitrophenyl;
• X is a bond or is selected from the group consisting of O, N, S, S(O), S(O2), N(R′), —C(O)N(R′)—, and —(CH2)mX1—;
• X1 is O, S, S(O), S(O2), or N(R′);
• R′ is H, alkyl, or aralkyl;
• Q represents independently for each occurrence H;
• OH;
• lower alkoxy;
• halo;
• mono-, di- or trihalomethyl;
• amino;
• lower alkylamino, or lower dialkylamino;
• U and V each represent independently for each occurrence O;
• NH;
• a lower alkylamino diradical;
• methylene;
• or mono- or dihalomethylene;
• Y2 and Y3 each represent independently for each occurrence O, O−;
• S−;
• or substituted or unsubstituted lower alkoxy, aryloxy, aralkyloxy, or cycloalkyloxy;
• M is H or a salt-forming cation;
• Z represents independently for each occurrence O, NH, or a lower alkylamino diradical;
• m and n are independently 0, 1 or 2;
• and
• W is P or S, provided that when W is S, Y3 is O.

A compound of Formula IIB:

• including enantiomers, diastereomers, enantiomerically enriched mixtures, racemic mixtures, prodrugs, crystalline forms, non-crystalline forms, amorphous forms, solvates, metabolites, and pharmaceutically acceptable salts thereof, wherein:
• Ar is aryl, alkyl, cycloalkyl, arylalkyl, or a heteroaryl or fused heteroaryl group containing 1-4 heteroatoms;
• each of which is optionally substituted with one or more of halo, hydroxy, alkyl, alkoxy, carboxy, cyano, nitro, sulfonamido, sulfonate, amino, alkylamino, or di-alkylamino;
• provided that when X is O, Ar is neither unsubstituted phenyl, anilino, nor 4-nitrophenyl;
• X is a bond or is selected from the group consisting of O, N, S, S(O), S(O2), N(R′), —C(O)N(R′)—, and —(CH2)mX1—;
• X1 is O, S, S(O), S(O2), or N(R′);
• R′ is H, alkyl, or aralkyl;
• Q represents independently for each occurrence H;
• OH;
• lower alkoxy;
• halo;
• mono-, di- or trihalomethyl;
• amino;
• lower alkylamino;
• or lower dialkylamino;
• U and V each represent independently for each occurrence O;
• NH;
• a lower alkylamino diradical;
• a lower dialkylamino diradical;
• methylene;
• or mono- or dihalomethylene;
• Y1 is CH2 or NH;
• Y2 and Y3 each represent independently for each occurrence O, O−;
• S−;
• or substituted or unsubstituted lower alkoxy, aryloxy, aralkyloxy, or cycloalkyloxy;
• M is H or a salt-forming cation;
• Z represents independently for each occurrence O, NH, or a lower alkylamino diradical;
• m and n are independently 0, 1 or 2;
• W is P or S, provided that when W is S, Y3 is O.

A compound of Formula IIIA:

• including enantiomers, diastereomers, enantiomerically enriched mixtures, racemic mixtures, prodrugs, crystalline forms, non-crystalline forms, amorphous forms, solvates, metabolites, and pharmaceutically acceptable salts thereof, wherein:
• is phenyl or pyridyl;
• X1 is O, NH, N(alkyl), —N(alkyl)-C(O)—, —C(O)N(alkyl)-, —N(alkyl)-CH2—, —CH2—N(alkyl)-, —CH2N(alkyl)-C(O)—, or —C(O)N(alkyl)-CH2—;
• R′ represents independently for each occurrence halo, hydroxy, alkyl, alkoxy, carboxy, cyano, nitro, sulfonamido, sulfonate, amino, alkylamino, or di-alkylamino;
• and
• t is 0, 1, 2, or 3.

A compound of Formula IV:

• including enantiomers, diastereomers, enantiomerically enriched mixtures, racemic mixtures, prodrugs, crystalline forms, non-crystalline forms, amorphous forms, solvates, metabolites, and pharmaceutically acceptable salts thereof, wherein:
• Ar is aryl, alkyl, cycloalkyl, aralkyl, or a heteroaryl or fused heteroaryl group containing 1-4 heteroatoms;
• each of which is optionally substituted with one or more of halo, hydroxy, alkyl, alkoxy, carboxy, cyano, nitro, sulfonamido, sulfonate, amino, alkylamino, or di-alkylamino;
• provided that when X is O, Ar is neither unsubstituted phenyl, anilino, nor 4-nitrophenyl;
• X is O, N, S, S(O), S(O2), N(R′), —C(O)N(R′)—, or —(CH2)mX1—;
• X1 is O, S, S(O), S(O2), or N(R′);
• R′ is H, alkyl, or aralkyl;
• Q represents independently for each occurrence H;
• OH;
• lower alkoxy;
• halo;
• mono-, di- or trihalomethyl;
• amino;
• lower alkylamino;
• or lower dialkylamino;
• U and V each represent independently for each occurrence O;
• NH;
• a lower alkylamino diradical;
• a lower dialkylamino diradical;
• methylene;
• or mono- or dihalomethylene;
• Y2 and Y3 each represent independently for each occurrence O, O−;
• S−;
• or substituted or unsubstituted lower alkoxy, aryloxy, aralkyloxy, or cycloalkyloxy;
• M is H or a salt-forming cation;
• Z represents independently for each occurrence O, NH, or a lower alkylamino diradical;
• m and n are independently 0, 1 or 2;
• and
• W is P or S, provided that when W is S, Y3 is O.