Patent ID: 6489476
Filing Date: 2002-12-03
Classification: A61P,C07F

Abstract:
A compound of formula (I): wherein R5 is selected from the group consisting of: wherein:each G is independently selected from the group consisting of C, N, O, S, and Se, and wherein no more than one G is O, S, or Se, and at most one G is N; each Gâ€² is independently selected from the group consisting of C and N and wherein no more than two Gâ€² groups are N; A is selected from the group consisting of â€”H, â€”NR42, â€”CONR42, â€”CO2R3, halo, â€”S(O)R3, â€”SO2R3, alkyl, alkenyl, alkynyl, perhaloalkyl, haloalkyl, aryl, â€”CH2OH, â€”CH2NR42, â€”CH2CN, â€”CN, â€”C(S)NH2, â€”OR3â€”SR3, â€”N3, â€”NHC(S)NR42, â€”NHAc, and nothing; each B and D are independently selected from the group consisting of â€”H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, alkoxyalkyl, â€”C(O)R11â€”C(O)SR3, â€”SO2R11â€”S(O)R3, â€”CN, â€”NR92, â€”OR3, â€”SR3, perhaloalkyl, halo, â€”NO2, and nothing, all except â€”H, â€”CN, perhaloalkyl, â€”NO2, and halo are substituted or unsubstituted; E is selected from the group consisting of â€”H, alkyl, alkenyl, alkynyl, aryl, alicyclic, alkoxyalkyl, â€”C(O)OR3, â€”CONR42, â€”CN, â€”NR92, â€”NO2, â€”OR3, â€”SR3, perhaloalkyl, halo, and nothing, all except â€”H, â€”CN, perhaloalkyl, and halo are substituted or unsubstituted; J is selected from the group consisting of â€”H and nothing; X is a substituted or unsubstituted linking group that links R5 to the phosphorus atom via 2-4 atoms, wherein 0-1 atoms are heteroatoms selected from N, O, and S, and the remaining atoms are carbon, except that if X is urea or carbamate there are 2 heteroatoms, measured by the shortest path between R5 and the phosphorus atom, and wherein the atom attached to the phosphorus is a carbon atom, and wherein there is no N in the linking group unless it is connected directly to a carbonyl or in the ring of a heterocycle; and wherein X is not a 2 carbon atom -alkyl- or -alkenyl- group; with the proviso that X is not substituted with â€”COOR2, â€”SO3R1, or â€”PO3R12; Y is independently selected from the group consisting of â€”Oâ€”, and â€”NR6â€”; when Y is â€”Oâ€”, then R1 attached to â€”Oâ€” is independently selected from the group consisting of â€”H, alkyl, substituted or unsubstituted aryl, substituted or unsubstituted alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, substituted or unsubstituted -alkylaryl, â€”C(R2)2OC(O)NR22, â€”NR2â€”C(O)â€”R3, â€”C(R2)2â€”OC(O)R3, â€”C(R2)2â€”Oâ€”C(O)OR3, â€”C(R2)2OC(O)SR3, -alkyl-Sâ€”C(O)R3, -alkyl-Sâ€”S-alkylhydroxy, and -alkyl-Sâ€”Sâ€”S-alkylhydroxy, when Y is â€”NR6â€”, then R1 attached to â€”NR6â€” is independently selected from the group consisting of â€”H, â€”[C(R2)2]qâ€”COOR3, â€”C(R4)2COOR3, â€”[C(R2)2]qâ€”C(O)SR3, and -cycloalkylene-COOR3; or when either Y is independently selected from â€”Oâ€” and â€”NR6â€”, then together R1 and R1 are -alkyl-Sâ€”S-alkyl- to form a cyclic group, or together R1 and R1 are whereinV, W, and Wâ€² are independently selected from the group consisting of â€”H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, wherein 0-1 atoms are heteroatoms and the remaining atoms are carbon, substituted with hydroxy, acyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both Y groups attached to the phosphorus; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, wherein 0-1 atoms are heteroatoms and the remaining atoms are carbon, that is fused to an aryl group at the beta and gamma position to the Y attached to the phosphorus; together V and W are connected via an additional 3 carbon atoms to form a substituted or unsubstituted 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 one of said carbon atoms that is three atoms from a Y attached to the phosphorus; together Z and W are connected via an additional 3-5 atoms to form a cyclic group, wherein 0-1 atoms are heteroatoms and the remaining atoms are carbon, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl; together W and Wâ€² are connected via an additional 2-5 atoms to form a cyclic group, wherein 0-2 atoms are heteroatoms and the remaining atoms are carbon, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl; Z is selected from the group consisting of â€”CHR2OH, â€”CHR2OC(O)R3, â€”CHR2OC(S)R3, â€”CHR2OC(S)OR3, â€”CHR2OC(O)SR3, â€”CHR2OCO2R3, â€”OR2, â€”SR2, â€”CHR2N3, â€”CH2aryl, â€”CH(aryl)OH, â€”CH(CH&boxH;CR22)OH, â€”CH(Câ‰¡CR2)OH, â€”R2, â€”NR22, â€”OCOR3, â€”OCO2R3, â€”SCOR3, â€”SCO2R3, â€”NHCOR2, â€”NHCO2R3, â€”CH2NHaryl, â€”(CH2)pâ€”OR2, and â€”(CH2)pâ€”SR2; p is an integer 2 or 3; q is an integer 1 or 2; with the provisos that: a) V, Z, W, Wâ€² are not all â€”H; and b) when Z is â€”R2, then at least one of V, W, and Wâ€² is not â€”H, alkyl, aralkyl, or alicyclic; R2 is selected from the group consisting of R3 and â€”H; R3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl; each R4 is independently selected from the group consisting of â€”H, and alkyl, or together R4 and R4 form a cyclic alkyl group; R6 is selected from the group consisting of â€”H, lower alkyl, acyloxyalkyl, alkoxycarbonyloxyalkyl, and lower acyl; each R9 is independently selected from the group consisting of â€”H, alkyl, aralkyl, and alicyclic, or together R9 and R9 form a cyclic alkyl group; R11 is selected from the group consisting of alkyl, aryl, â€”NR22, and â€”OR2; and with the provisos that: 1) when Gâ€² is N, then the respective A, B, D, or E is nothing; 2) at least one of A and B, or A, B, D, and E is not selected from the group consisting of â€”H or nothing; 3) when R5 is a six-membered ring, then X is not any 2 atom linker, a substituted or unsubstituted -alkyl-, a substituted or unsubstituted -alkenyl-, a substituted or unsubstituted -alkyloxy-, or a substituted or unsubstituted -alkylthio-; 4) when G is N, then the respective A or B is not halogen or a group directly bonded to G via a heteroatom; 5) R1 is not unsubstituted C1-C10 alkyl; 6) when X is not an -aryl- group, then R5is not substituted with two or more aryl groups; or pharmaceutically acceptable prodrugs or salts thereof.