NOVEL PRODRUGS FOR PHOSPHORUS-CONTAINING COMPOUNDS

摘要

Prodrugs of formula (I), their uses, their intermediates, and their method of manufacture are described, wherein V is selected from the group consisting of H, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, 1-alkynyl, and -R9; or together V and Z are connected via 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus; or together V and Z are connected via 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the oxygen attached to the phosphorus; or together V and W are connected via 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus; W and W' are independently selected from the group consisting of -H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, 1-alkynyl, and -R9; Z is selected from the group consisting of -CHR2OH, -CHR2OC(O)R3, -CHR2OC(S)R3, -CHR2OC(S)OR3, CHR2OC(O)SR3, -CHR2OCO2R3, -OR2, -SR2, -CHR2N3, -CH2aryl, -CH(aryl)OH, CH(CH=CR22)OH, -CH(C~CR2)OH, -R2, -NR22, -OCOR3, -OCO2R3, -SCOR3, -SCO2R3, NHCOR2, -NHCO2R3, -CH2NHaryl, -(CH2)p-OR2, and -(CH2)p-SR2; R2 is an R3 or -H; R3 is selected from the group consisting of alkyl, aryl, aralkyl, and alicyclic; and R9 is selected from the group consisting of alkyl, aralkyl, and alicyclic; p is an integer from 2 to 3; with the provisos that a) V, Z, W, and W' are not all -H; and b) when z is -R2, then at least one of V and W is not H, or -R9; and M is selected from the group that attached to PO32-, P2O63-, or P3O94- is biologically active in vivo, and that is attached to the phosphorus in formula (I) via a carbon, oxygen, or nitrogen atom; and pharmaceutically acceptable prodrugs and salts thereof.