Patent ID: 6130212
Filing Date: 2000-10-10
Classification: C07D,C07J

Abstract:
A method of treating cancers comprising administering an effective amount of at least one compound of the following formula: ##STR20## wherein: R.sup.1 is selected from a group consisting of: hydrogen; C.sub.1 -C.sub.6 alkyl; ar(C.sub.1 -C.sub.6)alkyl; ar(C.sub.1 -C.sub.6)alkyl substituted on aryl by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; aryl; aryl sustituted by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; --COR.sup.8 ; --COOR.sup.8 ; --CONH.sub.2 ; --(CH.sub.2).sub.p R.sup.10 ; and --(CH.sub.2).sub.p Vect;R.sup.2 is selected from the group consisting of: hydrogen; C.sub.1 -C.sub.6 alkyl; ar(C.sub.1 -C.sub.6)alkyl; ar(C.sub.1 -C.sub.6)alkyl substituted on aryl by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; aryl; aryl substituted by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl, --COR.sup.8 ; --COOR.sup.8 ; --CONH.sub.2 ; --CONR.sup.8 R.sup.9 ; --(CH.sub.2).sub.p R.sup.10 ; and --(CH.sub.2).sub.p Vect;R.sup.3 is selected from the group consisting of: hydrogen; C.sub.1 -C.sub.6 alkyl; ar(C.sub.1 -C.sub.6)alkyl; ar(C.sub.1 -C.sub.6)alkyl substituted on aryl by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; aryl; aryl substituted by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; --COR.sup.8 ; --COOR.sup.8 ; --CONH.sub.2 ; --CONR.sup.8 R.sup.9 ; --(CH.sub.2).sub.p R.sup.10 ; and --(CH.sub.2).sub.p Vect;R.sup.4 is selected from the group consisting of: --NO.sub.2 ; --NO; --CN; --COOR.sup.9 ; --SO.sub.3 R.sup.9 ; --CONR.sup.9 R.sup.11 and --SO.sub.2 NR.sup.9 R.sup.11 ;R.sup.5 is selected from the group consisting of: hydrogen; C.sub.1 -C.sub.6 alkyl; --COR.sup.8 ; --COOR.sup.8 ; --CONR.sup.8 R.sup.9 ; --(CH.sub.2).sub.p R.sup.10 ; --(CH.sub.2).sub.p Vect; --N.sup.+ R.sup.11.sub.3 Y.sup.- ; --CO.sub.3.sup.-Z.sup.+ and --CO.sub.2.sup.- Z.sup.+ ;X is selected from the group consisting of: (CR.sup.6 R.sup.7).sub.n ; and CO;R.sup.6 is selected from the group consisting of: hydrogen; C.sub.1 -C.sub.6 alkyl; --COR.sup.8 ; --COOR.sup.8 ; --CONR.sup.8 R.sup.9 ; --(CH.sub.2).sub.p R.sup.10 ; and --(CH.sub.2).sub.p Vect;R.sup.7 is selected from the group consisting of: hydrogen, C.sub.1 -C.sub.6 alkyl; --COR.sup.8 ; --COOR.sup.8 ; --CONR.sup.8 R.sup.9 ; --(CH.sub.2).sub.p R.sup.10 ; and --(CH.sub.2).sub.p Vect;R.sup.8 is selected from the group consisting of: C.sub.1 -C.sub.6 alkyl; ar(C.sub.1 -C.sub.6)alkyl; ar(C.sub.1 -C.sub.6)alkyl substituted on aryl by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; aryl; aryl sustituted by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; heteroaryl; heteroaryl substituted by one or more identical or different groups selected from: C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; and --(CH.sub.2).sub.p Vect;R.sup.9 is selected from the group consisting of: hydrogen; C.sub.1 -C.sub.6 alkyl; ar(C.sub.1 -C.sub.6)alkyl; ar(C.sub.1 -C.sub.6)alkyl substituted on aryl by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; aryl; aryl sustituted by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; and --(CH.sub.2).sub.p Vect;R.sup.10 is selected from the group consisting of: hydrogen; --N.sup.+ R.sup.11.sub.3 Y.sup.- ; --SO.sub.3.sup.- Z.sup.+ and --CO.sub.2.sup.- Z.sup.+ ;R.sup.11 is selected from the group consisting of: hydrogen; C.sub.1 -C.sub.6 alkyl; ar(C.sub.1 -C.sub.6)alkyl; ar(C.sub.1 -C.sub.6)alkyl substituted on aryl by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; aryl; aryl sustituted by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; ##STR21## W is either a single bond with --(CH.sub.2).sub.p --, or a heteroatom selected from the group consisting of O, N and S, bound to --(CH.sub.2).sub.p --;Y.sup.- is the anion of a pharmaceutically acceptable acid;Z.sup.+ is the cation of a pharmaceutically acceptable base;n=0 or 1;m=0 or 1;p=2 to 10;and their pharmaceutically acceptable salts of acids or bases; and a pharmaceutically acceptable carrier, excipient or vehicle;with the proviso that there can not be more than one Vect substituent within each molecule of said formula I, and with the further proviso that when R.sup.4 is --CN or --SO.sub.2 NR.sup.9 R.sup.11, eitherR.sup.5 is selected from the group consisting of --COR.sup.8 ; --COOR.sup.8 ; --CONR.sup.8 R.sup.9 ; --N.sup.+ R.sup.11.sub.3 Y.sup.- ; and --CO.sub.2.sup.- Z.sup.+ ;R.sup.1 is selected from a group consisting of: aryl; aryl sustituted by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; --COOR.sup.8 ; --CONH.sub.2 ; --CONR.sup.8 R.sup.9 ; and --(CH.sub.2).sub.p R.sup.10 ;R.sup.2 is selected from a group consisting of: aryl; aryl sustituted by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide; sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; --COOR.sup.8 ; --CONH.sub.2 ; --CONR.sup.8 R.sup.9 ; and --(CH.sub.2).sub.p R.sup.10 ; orR.sup.3 is selected from a group consisting of: aryl; aryl sustituted by one or more identical or different groups selected from C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, hydroxyl, nitro, amino, C.sub.1 -C.sub.6 alkylamino, di(C.sub.1 -C.sub.6 -alkyl)amino, sulfonyl, sulfonamide, sulfo(C.sub.1 -C.sub.6 -alkyl), --CO.sub.2 H, and --CO.sub.2 --(C.sub.1 -C.sub.6)alkyl; --COOR.sup.8 ; --CONH.sub.2 ; --CONR.sup.8 R.sup.9 ; and --(CH.sub.2).sub.p R.sup.10.