Patent ID: 6054587
Filing Date: 2000-04-25
Classification: C07F

Abstract:
A compound of formula 1: ##STR66## wherein: B is selected from the group consisting of --NH--, and --CH.dbd.;D is ##STR67## Q is selected from the group consisting of --C.dbd. and --N-- with the proviso that when B is --NH-- then Q is --C.dbd. and D is ##STR68## and when B is --CH.dbd. then Q is --N-- and D is ##STR69## A, E, and L are selected from the group consisting of --NR.sup.8 .sub.2 --NO.sub.2, --H, --OR.sup.7, --SR.sup.7, --C(O)NR.sup.4.sub.2, halo, --COR.sup.11, --SO.sub.2 R.sup.3, guanidine, amidine, --NHSO.sub.2 R.sup.5, --SO.sub.2 R.sup.4.sub.2, --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 E and J form a cyclic group including aryl, cyclic alkyl, and heterocyclic;J is selected from the group consisting of --NR.sup.8.sub.2, --NO.sub.2, --H, --OR.sup.7, --SR.sup.7, --C(O)NR.sup.4.sub.2, halo, --C(O)R.sup.11, --CN, sulfonyl, sulfoxide, perhaloalkyl, hydroxyalkyl, perhaloalkoxy, alkyl, haloalkyl, aminoalkyl, alkenyl, alkynyl, alicyclic, aryl, and aralkyl, or together with Y forms a cyclic group including 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, heteroaryl, carbonylalkyl, 1,1-dihaloalkyl, aminocarbonylamino, alkylaminoalkyl, alkoxyalkyl, alkylthioalkyl, alkylthio, alkylaminocarbonyl, alkylcarbonylamino, alicyclic, aralkyl, and alkylaryl, all optionally substituted by one to four substituents, independently selected from the group consisting of lower alkyl, lower aryl, lower aralkyl, lower alicyclic, hydroxy, lower alkoxy, lower aryloxy, perhaloalkoxy, aralkoxy, heteroaryl, heteroaryloxy, heteroarylalkyl, heteroaralkoxy, azido, amino, guanidino, haloen, lower alkylthio, oxa, ketone, carboxy esters, carboxyl, carboxamido, nitro, acyloxy, alkylamino, aminoalkyl, alkylaminoaryl, alkylaryl, alkylaminoalkyl, alkoxyaryl, arylamino, aralkylamino, phosphonate, sulfonate, carboxamidoalkylaryl, carboxamidoaryl, hydroxyalkyl, haloalkyl, alkylaminoalkylcarboxy, aminocarboxamidoalkyl, cyano, lower alkoxyalkyl, and lower perhaloalkyl; or together with Y forms a cyclic group including aryl, cyclic alkyl, and heterocyclic;Y is selected from the group consisting of --H, alkyl, alkenyl, alkynyl, aryl, alicyclic, aralkyl, aryloxyalkyl, alkoxyalkyl, --C(O)R.sup.3, --S(O).sub.2 R.sup.3, --C(O)--OR.sup.3, --CONHR.sup.3, --NR.sup.2.sub.2, --OR.sup.3, all except H are optionally substituted; or together with X forms a cyclic group including aryl, cyclic alkyl, and heterocyclic;R.sup.1 is independently selected from the group consisting of --H, alkyl, aryl, alicyclic where the cyclic moiety contains a carbonate or thiocarbonate, --C(R.sup.2).sub.2 -aryl, alkylaryl, --C(R.sup.2).sub.2 OC(O)NR.sup.2.sub.2, --NR.sup.2 --C(O)--R.sup.3, --C(R.sup.2).sub.2 --OC(O)R.sup.3, C(R.sup.2).sub.2 --O--C(O)OR.sup.3, --C(R.sup.2).sub.2 OC(O)SR.sup.3, alkyl-S--C(O)R.sup.3, alkyl-S--S-alkylhydroxy, and alkyl-S--S--S-alkylhydroxy, or together R.sup.1 and R.sup.1 are -alkyl-S--S-alkyl to form a cyclic group, or together R.sup.1 and R.sup.1 are ##STR70## wherein V and W are independently selected from the group consisting of hydrogen, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, 1-alkynyl, and --R.sup.9 ; ortogether 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; ortogether 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 --CH.sub.2 OH, --CH.sub.2 OCOR.sup.3, --CH.sub.2 OC(O)SR.sup.3, --CH.sub.2 OCO.sub.2 R.sup.3, --SR.sup.3, --S(O)R.sup.3, --CH.sub.2 N.sub.3, --CH.sub.2 NR.sup.2.sub.2, --CH.sub.2 Ar, --CH(Ar)OH, --CH(CH.dbd.CR.sup.2 R.sup.2)OH, --CH(C.tbd.--CR.sup.2)OH, and --R.sup.2 ;with the provisos that:a) V, Z, W are not all --H; andb) when Z is --R.sup.2, then at least one of V and W is not --H or --R.sup.9 ;R.sup.2 is selected from the group consisting of R.sup.3 and --H;R.sup.3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl;R.sup.4 is independently selected from the group consisting of --H, lower alkyl, lower alicyclic, lower aralkyl, and lower aryl;R.sup.5 is selected from the group consisting of lower alkyl, lower aryl, lower aralkyl, and lower alicyclic;R.sup.6 is independently selected from the group consisting of --H, and lower alkyl;R.sup.7 is independently selected from the group consisting of --H, lower alkyl, lower alicyclic, lower aralkyl, lower aryl, and --C(O)R.sup.10 ;R.sup.8 is independently selected from the group consisting of --H, lower alkyl, lower aralkyl, lower aryl, lower alicyclic, --C(O)R.sup.10, or together said R.sup.8 groups form a bidentate alkyl;R.sup.9 is selected from the group consisting of alkyl, aralkyl, and alicyclic;R.sup.10 is selected from the group consisting of --H, lower alkyl, --NH.sub.2, lower aryl, and lower perhaloalkyl;R.sup.11 is selected from the group consisting of alkyl, aryl, --OH, --NH.sub.2 and --OR.sup.3 ; andpharmaceutically acceptable prodrugs and salts thereof; with the provisos that:a) R.sup.1 is not lower alkyl of 1-4 carbon atoms;b) X is not alkylamine and alkylaminoalkyl substituted with phosphonic esters or acids;c) A, L, E, J, Y, and X together may only form 0-2 cyclic groups; andd) X is not aryl and alkylaryl linked 1,4 through a 6-membered aromatic ring.