Anti-cancer phosphonate analogs

A method of inhibiting leukemia cells in vitro comprising the step of contacting a sample in need of such treatment with a conjugate or a pharmaceutically acceptable salt or solvate thereof wherein the conjugate is a compound of the formula:

• [DRUG]−(A0)nn;
• wherein:
• DRUG is a compound of formula 557:
• wherein:
• nn is 1, 2 or 3;
• A0 is A1, A2 or W3 with the proviso that the conjugate includes at least one A1;
• 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 Y2 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 R2 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 Y1;
• 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;
• W3 is W4 or W5;
• W4 is R5, —C(Y1)R5, —C(Y1)W5, —SOM2R5, or —SOM2W5;
• W5 is carbocycle 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;
• and
• M12c is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.