Antiviral phosphonate analogs

A conjugate of the following formula:

• or a pharmaceutically acceptable salt or solvate thereof;
• wherein:
• B is selected from 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, substituted triazole, and pyrazolo[3,4-d]pyrimidine;
• X is selected from O, C(Ry)2, OC(Ry)2, NR and S;
• Z is independently selected from H, OH, OR, NR2, CN, NO2, SH, SR, F, Cl, Br, and I;
• Y1 is independently O, S, NR, +N(O)(R), N(OR), +N(O)(OR), or N—NR2;
• Y2 of the moiety
• is independently CR2, NR, +N(O)(R), N(OR), +N(O)(OR), N—NR2, S, S—S, S(O), or S(O)2;
• Y2 of the moiety
• is independently O, CR2, NR, +N(O)(R), N(OR), +N(O)(OR), N—NR2, S, S—S, S(O), or S(O)2;
• M2 is 0, 1 or 2;
• Ry is independently H, F, Cl, Br, I, OH, —C(═Y1)R, —C(═Y1)OR, —C(═Y1)N(R)2, —N(R)2, —+N(R)3, —SR, —S(O)R, —S(O)2R, —S(O)(OR), —S(O)2(OR), —OC(═Y1)R, —OC(═Y1)OR, —OC(═Y1)(N(R)2), —SC(═Y1)R, —SC(═Y1)OR, —SC(═Y1)(N(R)2), —N(R)C(═Y1)R, N(R)C(═Y1)OR, or —N(R)C(═Y1)N(R)2, amino (—NH2), ammonium (—NH3+), alkylamino, dialkylamino, trialkylammonium, C1-C8 alkyl, C1-C8 alkylhalide, carboxylate, sulfate, sulfamate, sulfonate, 5-7 membered ring sultam, C1-C8 alkylsulfonate, C1-C8 alkylamino, 4-dialkylaminopyridinium, C1-C8 alkylhydroxyl, C1-C8 alkylthiol, alkylsulfone (—SO2R), arylsulfone (—SO2Ar), arylsulfoxide (—SOAr), arylthio (—SAr), sulfonamide (—SO2NR2), alkylsulfoxide (—SOR), ester (—C(═O)OR), amido (—C(═O)NR2), 5-7 membered ring lactam, 5-7 membered ring lactone, nitrite (—CN), azido (—N3), nitro (—NO2), C1-C8 alkoxy (—OR), C1-C8 alkyl, C1-C8 substituted alkyl, C1-C8 alkenyl, C1-C8 substituted alkenyl, C1-C8 alkynyl, C1-C8 substituted alkynyl, C6-C20 aryl, C6-C20 substituted aryl, C2-C20 heterocycle, C2-C20 substituted heterocycle, polyethyleneoxy, or W3;
• or when taken together, Ry forms a carbocyclic ring of 3 to 7 carbon atoms;
• Rx is independently Ry, a protecting group, or the formula:
• wherein:
• 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;
• and
• R is C1-C8 alkyl, C1-C8 substituted alkyl, C1-C8 alkenyl, C1-C8 substituted alkenyl, C1-C8 alkynyl, C1-C8 substituted alkynyl, C6-C20 aryl, C6-C20 substituted aryl, C2-C20 heterocycle, C2-C20 substituted heterocycle, or a protecting group;
• and
• W3 is W4 or W5, where W4 is R, —C(Y1)Ry, —C(Y1)W5, —SO2Ry, or —SO2W5;
• and W5 is a carbocycle or a heterocycle wherein W5 is independently substituted with 0 to 3 Ry groups.