3′-deoxy nucleosides for the treatment of HCV

A compound according to formula III or IV:

• or a pharmaceutically acceptable salt, solvate, tautomeric form, or polymorphic form thereof, wherein:
• Ar1 is aryl or heteroaryl;
• R3 is alkyl;
• Base2 is
• or a tautomeric form thereof;
• R4 is hydrogen, hydroxyl, amino, or alkoxyl;
• R5 is hydrogen, hydroxyl, or alkoxyl;
• R6 is hydrogen, halogen, or alkyl;
• and
• Y is hydrogen, —OR1, —SR1, —NR1R2, or an N-linked amino acid, or ester thereof.

A compound according to Formula Ia or Ib:

• or a pharmaceutically acceptable salt, solvate, tautomeric form, or polymorphic form thereof, wherein:
• Base1 is
• or a tautomeric form thereof;
• Base2 is
• or a tautomeric form thereof;
• R4 is hydrogen, hydroxyl, —NH2, —O-(alkyl) or —O-(unsubstituted cycloalkyl);
• R5 is hydrogen, hydroxyl, or unsubstituted alkoxyl;
• R6 is hydrogen, halogen, or optionally substituted alkyl;
• R7 is hydrogen or —NH2;
• PD is hydrogen,
• W is S or O;
• each of X and Y is independently hydrogen, —OR1, —SR1, —NR1R2, an N-linked amino acid, or —NRX-G(SC)—C(O)-Q1;
• each Q1 is independently —SRY, —NRYRY, or alkoxyl;
• each RY is independently hydrogen or optionally substituted alkyl;
• each SC is independently a side chain of a naturally occurring or non-naturally occurring amino acid or is hydrogen, optionally substituted alkyl, arylalkyl, carboxylalkyl, heteroarylalkyl, aminoalkyl, hydroxylalkyl, aminoiminoaminoalkyl, aminocarbonylalkyl, sulfanylalkyl, carbamoylalkyl, alkylsulfanylalkyl, or hydroxylarylalkyl;
• each G is independently unsubstituted C1-C2 alkyl;
• each RX is independently hydrogen or RX and SC, together with the atoms to which they are attached, combine to form a five-membered heterocyclic ring;
• each R1 is independently hydrogen, optionally substituted alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl;
• and
• each R2 is independently hydrogen or optionally substituted alkyl;
• each alkyl is independently an unsubstituted C1 to C10 saturated hydrocarbon, unless specified otherwise;
• and when substituted is substituted with one or more moieties independently selected from halogen, hydroxyl, sulfanyl, —NR1′R2′ (wherein R1′ and R2′ are independently selected from hydrogen, alkyl, and cycloalkyl), —NH(alkyl), —N(alkyl)2, —NH(aryl), —N(aryl)2, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate;
• each alkoxy is —OR′ where each R′ is independently alkyl or cycloalkyl;
• and each alkoxy is independently optionally substituted, unless specified otherwise;
• each amino is —NR1′ R2′ or —NR1′, wherein R1′ and R2′ are independently selected from hydrogen, alkyl, and cycloalkyl;
• each aryl is independently phenyl, biphenyl, or naphthyl and is optionally substituted;
• and when substituted is substituted with one or more moieties independently selected from halogen, alkyl, haloalkyl, hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate;
• each cycloalkyl is an optionally substituted monocyclic saturated C3-15 hydrocarbon or a saturated, bridged or fused bicyclic C3-15 hydrocarbon;
• and when substituted is substituted with one or more moieties independently selected from halogen, hydroxyl, sulfanyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate;
• each heteroaryl is independently a monovalent monocyclic aromatic group with 5 to 20 ring atoms or multicyclic aromatic group that contains at least one aromatic ring with 5 to 20 ring atoms;
• wherein the monocyclic ring and at least one aromatic ring in the multicyclic ring contains one or more heteroatoms independently selected from O, S, and N in the ring provided that the total number of heteroatoms in each ring is four or less and each ring contains at least one carbon atom;
• wherein the heteroaryl is bonded to the rest of the molecule through the aromatic ring;
• and
• heterocyclic means a monovalent monocyclic non-aromatic ring system, or a bicyclic, tricyclic, or tetracyclic ring system which contains at least one non-aromatic ring and the other ring(s) may be partially saturate, fully saturated, or aromatic, and which bi-, tri- and tetracyclic ring can be fused or bridged;
• wherein one or more of the non-aromatic ring atoms is a heteroatoms independently selected from O, S, and N and the remaining ring atoms are carbon atoms and where the nitrogen or sulfur atoms may be optionally oxidized and the nitrogen atoms may be optionally quaternized;
• wherein the ring has 3 to 20 ring atoms;
• and wherein the heterocyclic is attached to the main structure at any heteroatom or carbon atom which results in the creation of a stable compound.