Substituted nucleoside and nucleotide analogs

A compound of Formula (II) or a pharmaceutically acceptable salt or a prodrug thereof:

• wherein:
• each is independently a double or single bond;
• A2 is selected from the group consisting of C (carbon), O (oxygen) and S (sulfur);
• B2 is an optionally substituted heterocyclic base or a derivative thereof;
• D2 is selected from the group consisting of C═CH2, CH2, O (oxygen), S (sulfur), CHF, and CF2;
• R19 is selected from the group consisting of hydrogen, an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted aralkyl, dialkylaminoalkylene, alkyl-C(═O)—, aryl-C(═O)—, alkoxyalkyl-C(═O)—, aryloxyalkyl-C(═O)—, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl,
• an —O-linked amino acid, diphosphate, triphosphate or derivatives thereof;
• R20 and R21 are independently selected from the group consisting of hydrogen, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl and an optionally substituted C1-6 haloalkyl, provided that at least one of R20 and R21 is not hydrogen;
• or R20 and R21 are taken together to form a group selected from among C3-6 cycloalkyl, C3-6 cycloalkenyl, C3-6 aryl, and a C3-6 heteroaryl;
• R22 and R27 is independently selected from the group consisting of hydrogen, halogen, —NH2, —NHRa2, NRa2Rb2, —ORa2, —SRa2, —CN, —NC, —N3, —NO2, —N(Rc2)—NRa2Rb2, —N(Rc2)—ORa2, —S—SRa2, —C(═O)Ra2, —C(═O)ORa2, —C(═O)NRa2Rb2, —O—C(═O)ORa2, —O—C(═O)NRa2Rb2, —N(Rc2)—C(═O)NRa2Rb2, —S(═O)Ra2, S(═O)2Ra2, —O—S(═O)2NRa2Rb2, —N(Rc2)—S(═O)2NRa2Rb2, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl and an —O-linked amino acid;
• R23, R24 and R25 are independently absent or selected from the group consisting of hydrogen, halogen, —NH2, —NHRa2, NRa2Rb2, —ORa2, —SRa2, —CN, —NC, —N3, —NO2, —N(Rc2)—NRa2Rb2, —N(Rc2)—ORa2, —S—SRa2, —C(═O)Ra2, —C(═O)ORa2, —C(═O)NRa2Rb2, —O—(C═O)Ra2, —O—C(═O)ORa2, —O—C(═O)NRa2Rb2, —N(Rc2)—C(═O)NRa2Rb2, —S(═O)Ra2, S(═O)2Ra2, —O—S (═O)2l NRa2Rb2, —N(Rc2)—S(═O)2NRa2Rb2, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an optionally substituted aralkyl and an —O-linked amino acid;
• or R24 and R25 taken together form —O—C(═O)—O—;
• R26 is absent or selected from the group consisting of hydrogen, halogen, —NH2, —NHRa2, NRa2Rb2, —ORa2, —SRa2, —CN, —NC, —N3, —NO2, —N(Rc2)—NRa2Rb2, —N(Rc2)—ORa2, —S—SRa2, —C(═O)Ra2, —C(═O)ORa2, —C(═O)NRa2Rb2, —O—C(═O)ORa2, —O—C(═O)NRa2Rb2, —N(Rc2)—C(═O)NRa2Rb2, —S(═O)Ra2, S(═O)2Ra2, —O—S(═O)2NRa2, Rb2, —N(Rc2)—S(═O)2NRa2Rb2, an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an optionally substituted haloalkyl, an optionally substituted hydroxyalkyl and an —O-linked amino acid, or when the bond to R25 indicated by is a double bond, then R25 is a C2-6 alkylidene and R26 is absent;
• Ra2, Rb2 and Rc2 are each independently selected from the group consisting of hydrogen, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl and an optionally substituted heteroaryl(C1-6 alkyl);
• R28 is selected from the group consisting of O−, —OH, an optionally substituted aryloxy or aryl-O—,
• alkyl-C(═O)—O—CH2—O—, alkyl-C(═O)—S—CH2CH2—O— and an —N-linked amino acid;
• R29 is selected from the group consisting of O−, −OH, aryloxy or aryl-O—,
• alkyl-C(═O)—O—CH2—O—, alkyl-C(═O)—S—CH2CH2—O— and an —N-linked amino acid;
• each R30 and each R31 are independently —C≡N or an optionally substituted substituent selected from the group consisting of C1-8 organylcarbonyl, C1-8 alkoxycarbonyl and C1-8 organylaminocarbonyl;
• each R32 is hydrogen or an optionally substituted C1-6-alkyl;
• each n is independently 1 or 2;
• and
• if both R28 and R29 are
• each R30, each R31, each R32 and each n can be the same or different.