Therapeutic phosphonate compounds

The conjugate oclaim 1 which has one of the following formulae:

• wherein:
• A0 is A1, A2 or W3 with the proviso that one A0 is A1;
• A1 is:
• A2 is:
• A3 is:
• Y1 is independently O, S, N(Rx), N(O)(Rx), N(ORx), N(O)(ORx), or N(N(Rx)(Rx));
• Y2 is independently a bond, O, N(Rx), N(O)(Rx), N(ORx), N(O)(ORx), N(N(Rx)(Rx)), —S(O)M2—, or —S(O))M2—S(O))M2—;
• and when Y joins two phosphorous atoms Y2 can also be C(R2)(R2);
• Rx is independently H, R1, R2, W3, a protecting group, or the formula:
• wherein:
• Ry is independently H, W3, R2 or a protecting group;
• R1 is independently H or alkyl of 1 to 18 carbon atoms;
• R2 is independently H, R1, R3 or R4 wherein each R4 is independently substituted with 0 to 3 R3 groups or taken together at a carbon atom, two R groups form a ring of 3 to 8 carbons and the ring may be substituted with 0 to 3 R3 groups;
• R3 is R3a, R3b, R3c or R3d, provided that when R3 is bound to a heteroatom, then R3 is R3c or R3d;
• R3a is F, Cl, Br, I, —CN, N3 or —NO2;
• R3b is Y;
• R3c is —Rx, —N(Rx)(Rx), —SRx, —S(O)Rx, —S(O)2Rx, —S(O)(ORx), —S(O)2(ORx), —OC(Y1)Rx, —OC(Y1)ORx, —OC(Y1)(N(Rx)(Rx)), —SC(Y1)Rx, —SC(Y1)ORx, —SC(Y1)(N(Rx)(Rx)), —N(Rx)C(Y1)Rx, —N(Rx)C(Y1)ORx, or —N(Rx)C(Y1)(N(Rx)(Rx));
• R3d is —C(Y1)Rx, —C(Y1)ORx or —C(Y1)(N(Rx)(Rx));
• R4 is an alkyl of 1 to 18 carbon atoms, alkenyl of 2 to 18 carbon atoms, or alkynyl of 2 to 18 carbon atoms;
• R5 is R4 wherein each R4 is substituted with 0 to 3 R3 groups;
• R5a is independently alkylene of 1 to 18 carbon atoms, alkenylene of 2 to 18 carbon atoms, or alkynylene of 2-18 carbon atoms any one of which alkylene, alkenylene or alkynylene is substituted with 0-3 R3 groups;
• W3 is W4 or W5;
• W4 is R5, —C(Y1)R5, —C(Y1)W5, —SO2R5, or —SO2W5;
• W5 is carbocycle or heterocycle wherein W5 is independently substituted with 0 to 3 R2 groups;
• W6 is W3 independently substituted with 1, 2, or 3 A3 groups;
• M2 is 0, 1 or 2;
• M12a is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;
• M12b is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;
• M1a, M1c, and M1d are independently 0 or 1;
• M12c is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;
• X51 is H, α-Br, or β-Br;
• X52 is alkyl or a arylalkyl;
• X53 is H, C1-C4 alkyl;
• X54 is CH or N;
• X55 is thymine, adenine, uracil, 5-halouracils, 5-alkyluracils, guanine, cytosine, 5-halo and alkyl cytosines, or 2,6-diaminopurine;
• X56 is H, Me, Et, or i-Pr;
• X57 is H or F;
• X58 is OH, C1, NH2, H, Me, or MeO;
• X59 is H or NH2;
• X60 is OH, C1, NH2, or H;
• X61 is H, NH2, or NH-alkyl;
• X62 and X63 are independently H, alkyl, or cyclopropyl;
• X64 is H, N3, NH2, or NHAc;
• X65 is a halo;
• X66 is alkoxy, aryloxy, alkenyloxy, arylalkoxy;
• X67 ═O or ═NH;
• X69 is H or alkyl;
• X82 is OH, F, or cyano;
• X83 is N or CH;
• X102 is thymine, adenine, guanine, cytosine, uracil, inosine, or diaminopurine;
• X103 is OH, alkoxy, CN, NO2, F, Cl, Br, or I;
• X104 is adenine, guanine, cytosine, uracil, thymine, 7-deazaadenine, 7-deazaguanine, 7-deaza-8-azaguanine, 7-deaza-8-azaadenine, inosine, nebularine, nitropyrrole, nitroindole, 2-aminopurine, 2-amino-6-chloropurine, 2,6-diaminopurine, hypoxanthine, pseudouridine, pseudocytosine, pseudoisocytosine, 5-propynylcytosine, isocytosine, isoguanine, 7-deazaguanine, 2-thiopyrimidine, 6-thioguanine, 4-thiothymine, 4-thiouracil, O6-methylguanine, N6-methyladenine, O4-methylthymine, 5,6-dihydrothymine, 5,6-dihydrouracil, 4-methylindole, or pyrazolo[3,4-d]pyrimidine;
• and
• X105 is cytosine.