Heterocyclic anti-viral compounds comprising metabolizable moieties and their uses

A compound according to structural formula

• A—B—C−(C(O))s—N(R11)—C(O)—CX2—R12
• or a pharmaceutically acceptable salt, hydrate, solvate or N-oxide thereof, wherein
• A is a phenyl or six-membered heteroaryl ring having from one to five of the same or different R20 substituents, provided that at least one of the substituents is positioned at the ortho position;
• B is a saturated, unsaturated, or aromatic heteroatomic ring having from one to three annular heteroatoms selected from N, O, and S, where the A and C moieties are attached to non-adjacent ring atoms of B, provided that when the B includes more than one annular oxygen atom, the oxygen atoms are not adjacent;
• C is a phenyl or a heteroaryl ring, wherein when C is phenyl, it is substituted relative to the B moiety at the meta position with the —(C(O))1—N(R11)—C(O)—CX2—R12, or when C is a heteroaryl group, the B moiety and the -(C(O))1—N(R11)—C(O)—CX2—R12 moiety are positioned on C with only one ring atom of C between them;
• s is 0 or 1;
• R11 is selected from the group consisting of hydrogen, lower alkyl, -(CHR10)n—J—G, or a group of the formula
• each X is independently H or halo, provided both X are not H;
• R12 is selected from the group consisting of hydrogen, —O—C(O)-alkyl, —C(O)OR16, —C(O)R17 and —P(O)(OR18)OR19;
• R15 is lower alkyl, arylalkyl, aryl, substituted cycloheteroalkyl, cycloheteroalkyl, substituted cycloalkyl, cycloalkyl, —C(O)OR18 or —CH2—OR30;
• R30 is hydrogen, lower alkyl or a sugar moiety;
• R16 is selected from the group consisting of aryl-C1-C6 alkyl, aryl, substituted cycloheteroalkyl, cycloheteroalkyl, substituted cycloalkyl, cycloalkyl, —C(O)OR16 or —CH2—OR30, (C1-15) alkyl and (C7-15) arylalkyl;
• R17 is selected from the group consisting of lower alkyl, —N(Rc)2, N-morpholino, N-piperazino and N-pyrrolidino;
• each Rc is independently Rb or alternatively, the both Rc taken together with the nitrogen atom to which they are bonded form a 5-, 6- or 7-membered cycloheteroalkyl which optionally includes from 1 to 4 of the same or different additional heteroatoms selected from the group consisting of O, N and S;
• each Rb is independently hydrogen or Ra;
• Ra is selected from the group consisting of alkyl, hydroxyalkyl, cycloalkyl, heteroalkyl, C0-C6 alkyl-cycloheteroalkyl, substituted C0-C6 alkyl-cycloheteroalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl;
• R18 is H, lower alkyl, aryl or arylalkyl;
• R19 is H, lower alkyl, aryl or arylalkyl;
• n is 0, 1, 2, 3 or 4;
• each R10 is independently hydrogen or lower alkyl;
• J is selected from the group consisting of -(CH2)1-3-, —O—, —O—(CH2)1-3-, —CH(OH)-, −C(═O)-, —S(O)m-, —C(═NR23)-, —C(═NOR29)-, —C(N—N—(R25)2)-, —C(N−NR27C(═O)N—(R27)2)- and —C(Z—R28)2-;
• m is 0, 1, or 2;
• R23 is selected from the group consisting of hydrogen, lower alkyl, aryl, substituted aryl, arylalkyl and substituted arylalkyl;
• R29 is selected from the group consisting of hydrogen, lower alkyl, aryl, substituted aryl, arylalkyl and substituted arylalkyl;
• each R25 is independently selected from the group consisting of hydrogen, lower alkyl, aryl, substituted aryl, arylalkyl and substituted arylalkyl;
• each R27 is independently selected from the group consisting of hydrogen, lower alkyl, aryl, substituted aryl, arylalkyl and substituted arylalkyl;
• each Z is independently —O— or —S—;
• each R28 is independently selected from the group consisting of lower alkyl, aryl, substituted aryl, arylalkyl and substituted arylalkyl or alternatively, the two R18's taken together with the heteroatoms to which they are bonded form a 5, 6 or 7 membered cycloheteroalkyl;
• G is selected from the group consisting of aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, cycloheteroalkyl and substituted cycloheteroalkyl;
• and
• each R20 is, independently of the other, selected from the group consisting of —OH, —SH, —CN, —C(O)H, —NO2, halo, fluoro, chloro, bromo, iodo, lower alkyl, substituted lower alkyl, lower heteroalkyl, substituted lower heteroalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, lower haloalkyl, monohalomethyl, dihalomethyl, trihalomethyl, trifluoromethyl, lower alkylthio, substituted lower alkylthio, lower alkoxy, substituted lower alkoxy, methoxy, substituted methoxy, lower heteroalkoxy, substituted lower heteroalkoxy, cycloalkoxy, substituted cycloalkoxy, cycloheteroalkoxy, substituted cycloheteroalkoxy, lower haloalkoxy, monohalomethoxy, dihalomethoxy, trihalomethoxy, trifluoromethoxy, amino, lower di- or monoalkylamino, substituted lower di- or monoalkylamino, aryl, substituted aryl, aryloxy, substituted aryloxy, phenoxy, substituted phenoxy, arylalkyl, substituted arylalkyl, arylalkyloxy, substituted arylalkyloxy, benzyl, benzyloxy, heteroaryl, substituted heteroaryl, heteroaryloxy, substituted heteroaryloxy, heteroarylalkyl, substituted heteroarylalkyl, heteroarylalkyloxy, substituted heteroarylalkyloxy, carboxyl, lower alkoxycarbonyl, substituted lower alkoxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, arylalkyloxycarbonyl, substituted arylalkyloxycarbonyl, carbamate, substituted carbamate, carbamoyl, substituted carbamoyl, thiocarbamoyl, substituted thiocarbamoyl, ureas, substituted ureas, thioureas, substituted thioureas, sulfamoyl, substituted sulfamoyl and a group of the formula —L—R14, where “L” is a linker and R14 is cycloalkyl, substituted cycloalkyl, cycloheteroalkyl or substituted cycloheteroalkyl;
• provided that when R11 is hydrogen or lower alkyl, then R12 is not hydrogen.