Patent ID: 6284748
Filing Date: 2001-09-04
Classification: A61P,C07F

Abstract:
A compound of formula 1: ##STR21##whereinA is selected from the group consisting of --NR.sup.8.sub.2, --NHSO.sub.2 R.sup.3, --OR.sup.5, --SR.sup.5, halo, lower alkyl, --CON(R.sup.4).sub.2, guanidino, amidino, --H, and perhaloalkyl;E is selected from the group consisting of --H, halo, lower alkylthio, lower perhaloalkyl, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, --CN, and --NR.sup.7.sub.2 ;X is selected from the group consisting of -alk-NR--, alkylene, alkenylene, alkynylene, arylene, heteroarylene, -alk-NR-alk-, -alk-O-alk-, -alk-S-alk-, -alk-S--, alicyclicene, heteroalicyclicene, 1,1-dihaloalkylene, --C(O)-alk-, --NR--C(O)--NR'--, -alk-NR--C(O)--, -alk-C(O)--NR--, -Ar-alk-, and -alk-Ar-, all optionally substituted, wherein each R and R' is independently selected from --H and lower alkyl, and wherein each ""alk"" and ""Ar"" is an independently selected alkylene or arylene, respectively;Y is selected from the group consisting of --H, alkyl, alkenyl, alkynyl, aryl, alicyclic, heteroalicyclic, 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, and --OR.sup.3, all except H are optionally substituted;R.sup.1 is independently selected from the group consisting of --H, alkyl, aryl, heteroalicyclic where the cyclic moiety contains a carbonate or thiocarbonate, --C(R.sup.2).sub.2 -aryl, -alk-aryl, --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, -alk-S--C(O)R.sup.3, -alk-S--S-alkylhydroxy, and -alk-S--S--S-alkylhydroxy, or together R.sup.1 and R.sup.1 are -alk-S--S-alk- to form a cyclic group, wherein each ""alk"" is an independently selected alkylene, or together R.sup.1 and R.sup.1 are ##STR22##whereinV 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 via a chain of 3-5 atoms, only one of which can be a heteroatom, to form part of a cyclic group 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 via a chain of 3 carbon atoms to form part of a cyclic group substituted with hydroxy, acyloxy, alkoxycarboxy, alkylthiocarboxy, hydroxymethyl, or 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.ident.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.sub.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, heteroalicyclic, and aralkyl;R.sup.4 is independently selected from the group consisting of --H, lower alkyl, lower alicyclic, lower heteroalicyclic, lower aralkyl, and lower aryl;R.sup.5 is selected from the group consisting of lower alkyl, lower aryl, lower aralkyl, lower alicyclic, and lower heteroalicyclic;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 heteroalicyclic, 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 bidendate alkylene;R.sup.9 is selected from the group consisting of alkyl, aralkyl, alicyclic, and heteroalicyclic;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.