Patent ID: 6399782
Filing Date: 2002-06-04
Classification: A61P,C07F

Abstract:
A pharmaceutical composition comprising a compound of formula (I): wherein: A, E, and L are selected from the group consisting of â€”NR82, â€”NO2, â€”H, â€”OR7, â€”SR7, â€”C(O)NR42, halo, â€”COR11, â€”SO2R3, guanidine, amidine, â€”NHSO2R5, â€”SO2NR42, â€”CN, sulfoxide perhaloacyl, perhaloalkyl, perhaloalkoxy, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, and lower alicyclic, or together A and L form a cyclic group, or together L and E form a cyclic group, or together A and J form a cyclic group selected from the group of aryl, cyclic alkyl, and heterocyclic; J is selected from the group consisting of â€”NH82, â€”NO2, â€”H, â€”OR7, â€”SR7, â€”C(O)NR42, halo, â€”C(O)R11, â€”CN, sulfonyl, sulfoxide, perhaloalkyl, hydroxyalkyl, perhaloalkoxy, alkyl, haloalkyl, aminoalkyl, alkenyl, alkynyl, alicyclic, aryl, and aralkyl, or together with Y forms a cyclic group selected from the group of aryl, cyclic alkyl and heterocyclic alkyl; X is selected from the group consisting of alkylamino, alkyl(hydroxy), alkyl(carboxyl), alkyl(phosphonate), alkyl, alkenyl, alkynyl, alkyl(sulfonate), aryl, carbonylalkyl, 1,1-dihaloalkyl, aminocarbonylamino, alkylaminoalkyl, alkoxyalkyl, alkylthioalkyl, alkylthio, alkylaminocarbonyl, alkylcarbonylamino, alicyclic, aralkyl, and alkylaryl, all optionally substituted; or together with Y forms a cyclic group selected from the group of aryl, cyclic alkyl, and heterocyclic; Y is selected from the group consisting of â€”H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, aryloxyalkyl, alkoxyalkyl, â€”C(O)R3, â€”S(O)2R3, â€”C(O)â€”R11, â€”CONHR3, NR22, and â€”OR3, all except â€”H are optionally substituted; or together with X form a cyclic group selected from the group of aryl, cyclic alkyl, and heterocyclic; R1 is independently selected from the group consisting of â€”H, alkyl, aryl, alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, â€”C(R2)2-aryl, alkylaryl, â€”C(R2)2OC(O)NR22, â€”NR2â€”C(O)â€”R3, â€”C(R2)2â€”OC(O)R3, 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, or together R1 and R1 are -alkyl-Sâ€”S-alkyl to form a cyclic group, or together R1 and R1 are wherein V and W are independently selected from the group consisting of hydrogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, 1-alkynyl, and â€”R9; or together V and Z are connected to form a cyclic group containing 3-5 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarboxy, or aryloxycarboxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus; or together V and W are connected to form a cyclic group containing 3 carbon atoms substituted with hydroxy, acyloxy, alkoxycarboxy, alkylthiocarboxy, hydroxymethyl, and aryloxycarboxy attached to a carbon atom that is three atoms from an oxygen attached to the phosphorus; Z is selected from the group consisting of â€”CH2OH, â€”CH2OCOR3, â€”CH2OC(O)SR3, â€”CH2OCO2R3, â€”SR3, â€”S(O)R3, â€”CH2N3, â€”CH2NR22, â€”CH2Ar, â€”CH(Ar)OH, â€”CH(CH&boxH;CR2R2)OH, â€”CH(Câ‰¡CR2)OH, and â€”R2; with the provisos that: a) V, Z, W, are not all â€”H; and b) when Z is â€”R2, then at least one of V and W is not â€”H or â€”R9; 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; R4 is independently selected from the group consisting of â€”H, lower alkyl, lower alicyclic, lower aralkyl, and lower aryl; R5 is selected from the group consisting of lower alkyl, lower aryl, lower aralkyl, and lower alicyclic; R6 is independently selected from the group consisting of â€”H, and lower alkyl; R7 is independently selected from the group consisting of â€”H, lower alkyl, lower alicyclic, lower aralkyl, lower aryl, and â€”C(O)R10; R8 is independently selected from the group consisting of â€”H, lower alkyl, lower aralkyl, lower aryl, lower alicyclic, â€”C(O)R10, or together they form a bidentate alkyl; R9 is selected from the group consisting of alkyl, aralkyl, and alicyclic; R10 is selected from the group consisting of â€”H, lower alkyl, â€”NH2, lower aryl, and lower perhaloalkyl; R11 is selected from the group consisting of alkyl, aryl, â€”OH, â€”NH2 and â€”OR3; and pharmaceutically acceptable prodrugs and salts thereof; and a pharmaceutically acceptable excipient; with the provisos that: a) R1 is not lower alkyl of 1-4 carbon atoms b) when X is alkyl or alkene, then A is â€”N(R82); c) X is not alkylamine and alkylaminoalkyl substituted with phosphonic esters and acids; and d) A, L, E, J, Y, and X together may only form 0-2 cyclic groups.