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Claims for Patent: RE42376

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Claims for Patent: RE42376

Title:Substituted 3-cyanoquinolines
Abstract: This invention provides compounds of formula I having the structure ##STR00001## wherein G.sub.1, G.sub.2, R.sub.1, R.sub.4, Z, n, and X are defined in the specification or a pharmaceutically acceptable salt thereof which are useful as antineoplastic agents and in the treatment of polycystic kidney disease.
Inventor(s): Wissner; Allan (Ardsley, NY), Tsou; Hwei-Ru (New City, NY), Berger; Dan M. (New City, NY), Floyd, Jr.; Middleton B. (Suffern, NY), Hamann; Philip R. (Thiells, NY), Zhang; Nan (Bayside, NY), Frost; Philip (Morris Township, NJ)
Assignee: Wyeth Holdings Corporation (Madison, NJ)
Application Number:12/785,269
Patent Claims: 1. A compound of Formula 1 having the structure: ##STR00044## wherein: X is cycloalkyl of 3 to 7 carbon atoms, which may be optionally substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a pyridinyl, pyrimidinyl, or phenyl ring wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalky of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, methylmercapto, and benzoylamino; Z is --NH--, --O--, --S--, or --NR--; R is alkyl of 1-6 carbon atoms, or carboalkyl of 2-7 carbon atoms; G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR00045## R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.k--Y--, R.sub.7--(C(R.sub.6).sub.2).sub.g--Y--, R.sub.7--(C(R.sub.6).sub.2).sub.pM--(C(R.sub.6).sub.2).sub.k--Y--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.k--Y-- with the proviso that either G.sub.1 or G.sub.2 or both G.sub.1 and G.sub.2 must be a radical selected from the group ##STR00046## R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.k--Y--, R'.sub.7--C(R.sub.6).sub.2).sub.g--Y--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.k--Y--, Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.k--Y--, or ##STR00047## Y is a divalent radical selected from the group consisting of ##STR00048## R.sub.7 is --NR.sub.6R.sub.6, --J, --OR.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6(OR.sub.6); R'.sub.7 is --N(OR.sub.6), --N(R.sub.6).sub.3.sup.+, alkenoxy of 1-6 carbon atoms, alkynoxy of 1-6 carbon atoms, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, N-alkyl-N-alkynylamino of 4 to 12 carbon atoms, N-alkenyl-N-alkynylamino of 4 to 12 carbon atoms, or N,N-dialkynylamino of 6-12 carbon atoms with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.pNR.sub.6R.sub.6, or >N--(C(R.sub.6).sub.2).sub.p--OR.sub.6; W is >NR.sub.6, --O-- or is a bond; Het is a heterocycle selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, pyridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, thiazole, thiazolidine, tetrazole, piperazine, furan, thiophene, tetrahydrothiophene, tetrahydrofuran, dioxane, 1,3-dioxolane, tetrahydropyran, and ##STR00049## wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.SOR.sub.6 or --(C(R.sub.6).sub.2).sub.SN(R.sub.6).sub.2, or optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.SO--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; R.sub.2, is selected from the group consisting of ##STR00050## ##STR00051## R.sub.3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR00052## R.sub.7--(C(R.sub.6).sub.2).sub.s--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.r--, R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.r, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r--; with the proviso that at least one of the R.sub.3 groups is selected from the group ##STR00053## R'.sub.7--(C(R.sub.6).sub.2).sub.s--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.r--, R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.r--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r--; with the proviso that for said at least one R.sub.3 group the moiety Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2)r-- cannot be morpholino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, piperidino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, N-alkyl piperidino-N-alkyl wherein either alkyl group is 1-6 carbon atoms, or azacycloalkyl-N-alkyl of 3-11 carbon atoms; R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR00054## R.sub.7--(C(R.sub.6).sub.2).sub.s--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.r--, R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.r--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r--; R.sub.8, and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.rNR.sub.6R.sub.6, or --(C(R.sub.6).sub.2).sub.rOR.sub.6; J is independently hydrogen, chlorine, fluorine, or bromine; Q is alkyl of 1-6 carbon atoms or hydrogen; a=0 or 1; g=1-6; k=0-4; n is 0-1; p=2-4; q=0-4; r=1-4; s=1-6; u 0-4 and v=0-4, wherein the sum of u+v is 2-4; or a pharmaceutically acceptable salt thereof, provided that when R.sub.6 is alkenyl of 2-7 carbon atoms or alkynyl of 2-7 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6-- and R.sub.7 is --NR.sub.6R.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6(OR.sub.6), then g 2-6; when M is --O-- and R.sub.7 is --OR.sub.6, then p=1-4; when Y is --NR.sub.6--, then k=2-4; when Y is --O-- and M or W is --O--, then k=1-4; when W is not a bond with Het bonded through a nitrogen atom, then q=2-4; and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6--, then k=2-4..].

.[.2. The compound according to claim 1 wherein Z is --NH-- and n=0 or a pharmaceutically acceptable salt thereof..].

.[.3. The compound according to claim 2 wherein X is optionally substituted phenyl or a pharmaceutically acceptable salt thereof..].

.[.4. The compound according to claim 3 wherein R.sub.1 and R.sub.4 are hydrogen or a pharmaceutically acceptable salt thereof..].

5. .[.The.]. .Iadd.A .Iaddend.compound .[.according to claim 1.]., which is: a) 1-Methyl-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid[4-(3-bromo-phenylamino)-3-cyano-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; b) N-[4-[(3-Bromophenyl)amino]-3-cyano-6-quinolinyl]-4-(N-allyl-N-methylamin- o)-2-butynamide or a pharmaceutically acceptable salt thereof; c) N-[4-[(3-Bromophenyl)amino]-3-cyano-6-quinolinyl]-4-(N-methoxyethyl-N-met- hylamino)-2-butynamide or a pharmaceutically acceptable salt thereof; d) N-[4-[(3-Bromophenyl)amino]-3-cyano-6-quinolinyl]-4-(bis-(2-methoxyethyl)- amino)-2-butynamide or a pharmaceutically acceptable salt thereof; e) 4-Methoxymethoxy-but-2-ynoic acid[4-(3-bromo-phenylamino)-3-cyano-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; f) 4-(4-Chloro-2-fluoro-phenylamino)-6-methoxy-7-(2-pyridin-4-yl-ethoxy)-1-q- uinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; g) 4-(2-Methoxy-ethoxy)-but-2-ynoic acid[4-(3-bromo-phenylamino)-3-cyano-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; h) .[.4-((2S)-2-Methoxymethylpyrrolidin-1-yl)but-2-ynoic Acid[4-(3-bromophenylamino)-3-cyanoquinolin-6-yl] amide.]. .Iadd.4-((2S)-2-Methoxymethylpyrrolidin-1-yl)but-2-ynoic acid[4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]-amide .Iaddend.or a pharmaceutically acceptable salt thereof; i) .[.4-(1,4-Dioxa-8-azaspiro[4,5]dec-8-yl)but-2-ynoic Acid [4-(3-Bromophenylamino)-3-cyanoquinolin-6-yl]amide.]. .Iadd.4-(1,4-Dioxa-8-azaspiro[4,5]dec-8-yl)but-2-ynoic acid[4-(3-Bromophenylamino)-3-cyanoquinolin-6-yl]-amide .Iaddend.or a pharmaceutically acceptable salt thereof; j) .[.4-(3-Bromo-phenylamino)-6-(2-ethoxy-3,4-dioxo-cyclobut-1-enylamino)-qu- inoline-3-carbonitrile.]. .Iadd.4-(3-Bromo-phenylamino)-6-[(2-ethoxy-3,4-dioxo-cyclobut-1-enyl]amin- o)-quinoline-3-carbonitrile .Iaddend.or a pharmaceutically acceptable salt thereof; k) .[.4-[(2-Methoxy-ethyl)-methyl-amino]-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide- .]. .Iadd.4-[(2-Methoxyethyl)(methyl)amino]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide .Iaddend.or a pharmaceutically acceptable salt thereof; l) (S)-4-(2-Methoxymethyl-pyrrolidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide dihydrochloride or a pharmaceutically acceptable salt thereof; m) 4-(3-Hydroxymethyl-piperidin-1-yl)-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; n) 4-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; o) 4-(2-Hydroxymethyl-piperidin-1-yl)-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; p) 4-Bromo-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; q) 4-(3-hydroxy-4-methyl-phenylamino)-6-methoxy-7-(3-pyridin-4-yl-propoxy)-q- uinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; r) .[.4-Diallylamino-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3cyano-7-methoxy-quinolin-6-yl]-am- ide.]. .Iadd.4-Diallylamino-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide .Iaddend.or a pharmaceutically acceptable salt thereof; s) 4-[Bis-(2-methoxy-ethyl)-amino]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; t) .[.4-([1,3]Dioxolan-2-ylmethyl-methyl-amino)-but-2-enoic acid3-cyano-7-methoxy-quinolin-6-yl]-amide.]. .Iadd.4-[([1,3]Dioxolan-2-yl-methyl)(methyl)amino]-but-2-enoic acid[3-cyano-7-methoxy-quinolin-6-yl]-amide .Iaddend.or a pharmaceutically acceptable salt thereof; u) 4-[Bis-(2-hydroxy-ethyl)-amino]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; v) 4-Thiomorpholin-4-yl-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; w) 4-[4-(2-Hydroxy-ethyl)-piperazin-1-yl]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; x) 4-(1,4,7-Trioxa-10-aza-cyclododec-10-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; y) .[.4-(Methoxy-methyl-amino)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide.]. .Iadd.4-[(Methoxy)(methyl)amino]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide .Iaddend.or a pharmaceutically acceptable salt thereof; z) 4-(4-Hydroxy-piperidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; aa) 4-[1,4']Bipiperidinyl-1'-yl-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; bb) 4-Thiazolidin-3-yl-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; cc) 3-{3-[4-(3-Chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-ylca- rbamoyl]-allyl}-4-methyl-thiazol-3-ium bromide or a pharmaceutically acceptable salt thereof; dd) 4-(2,6-Dimethyl-piperidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; ee) 4-[Bis-(2-hydroxy-propyl)-amino]-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; ff) 4-(3-Hydroxy-pyrrolidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; gg) .[.4-[(2-Hydroxy-ethyl)-methyl-amino]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide.]. .Iadd.4-[(2-Hydroxyethyl)(methyl)amino]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide .Iaddend.or a pharmaceutically acceptable salt thereof; hh) 4-(2,5-Dimethyl-pyrrolidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; ii) 4-(4,4-Dihydroxy-piperidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-a- mide or a pharmaceutically acceptable salt thereof; jj) 4-(3-Chloro-4-fluoro-phenylamino)-7-methoxy-6-pyrrolidin-1-yl-quinoline-3- -carbonitrile or a pharmaceutically acceptable salt thereof; kk) 4-(3-Chloro-4-fluroanilino)-7-methoxy-6-(1H-pyrrol-1-yl)-3-quinolinecarbo- nitrile or a pharmaceutically acceptable salt thereof; ll) 6-(1-Aziridinyl)-4-(3-chloro-4-fluoroanilino)-7-methoxy-3-quinolinecarbon- itrile or a pharmaceutically acceptable salt thereof; mm) .[.4-[(2-Methoxy-ethyl)-methyl-amino]-but-2-enoic acid[4-(3-bromo-phenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide.]. .Iadd.4-[(2-Methoxyethyl)(methyl)amino]-but-2-enoic acid[4-(3-bromo-phenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide .Iaddend.or a pharmaceutically acceptable salt thereof; nn) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-[3-(4-hydroxy-piperidin-1-yl)-pr- opoxy]-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; oo) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-{3-[4-(2-hydroxy-ethyl)-piperazi- n-1-yl]-propoxy}-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; pp) .[.4-(2-Bromo-4-chloro-phenylamino)-7-{2-[(2-hydroxy-ethyl)-methyl-amino]- -ethoxy}-6-methoxy-quinoline-3-carbonitrile.]. .Iadd.4-(2-Bromo-4-chloro-phenylamino)-7-{2-[(2-hydroxyethyl)(methyl)amin- o]-ethoxy}-6-methoxy-quinoline-3-carbonitrile .Iaddend.or a pharmaceutically acceptable salt thereof; qq) .[.4-(2,4-Dichloro-5-methoxy-phenylamino)-7-{3-[(2-hydroxy-ethyl)-methyl-- amino]-propoxy}-6-methoxy-quinoline-3-carbonitrile.]. .Iadd.4-(2,4-Dichloro-5-methoxy-phenylamino)-7-{3-[(2-hydroxyethyl)(methy- l)amino]-propoxy}-6-methoxy-quinoline-3-carbonitrile .Iaddend.or a pharmaceutically acceptable salt thereof; rr) 4-(2,4-Dichloro-5-methoxy-phenylamino)-6-methoxy-7-(3-thiomorpholin-4-yl-- propoxy)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ss) 4-(2,4-Dichloro-5-methoxy-phenylamino)-6-methoxy-7-[3-(2-methoxy-ethylami- no)-propoxy]-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; tt) 4-(2,4-Dichloro-5-methoxy-phenylamino)-6-methoxy-7-[3-(4-methyl-piperidin- -1-yl)-propoxy]-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; uu) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-[3-(2,6-dimethyl-morpholin-4-yl)- -propoxy]-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; vv) 4-(2-Bromo-4-chloro-phenylamino)-7-{2-[4-(2-hydroxy-ethyl)-piperazin-1-yl- ]-ethoxy}-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ww) 4-(2-Bromo-4-chloro-phenylamino)-7-[2-(4-hydroxy-piperidin-1-yl)-ethoxy]-- 6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; xx) 4-(2-Bromo-4-chloro-phenylamino)-6-methoxy-7-(2-thiomorpholin-4-yl-ethoxy- )-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; yy) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-[3-(2,5-dimethyl-pyrrolidin-- 1-yl)-propoxy]-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; zz) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-[3-(3-hydroxy-propylamino)-propo- xy]-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; aaa) .[.1-{3-[3-Cyano-4-(2,4-dichloro-5-methoxy-phenylamino)-6-methoxy-quinoli- n-7-yloxy]-propyl}-piperidine-4-carboxylic acid ethyl ester.]. .Iadd.1-{3-[3-Cyano-4-(2,4-dichloro-5-methoxy-phenylamino)-6-methoxy-quin- olin-7-yl-oxy]-propyl}-piperidine-4-carboxylic acid ethyl ester .Iaddend.or a pharmaceutically acceptable salt thereof; bbb) 7-[3-(4-acetyl-1-piperazinyl)propoxy]-4-[(2,4-dichloro-5-methoxyphenyl)am- ino]-6-methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ccc) .[.4-(3-chloro-4-fluoroanilino)-7-methyoxy-6(4-morpholinyl)-3-quinolineca- rbonitrile.]. .Iadd.4-(3-Chloro-4-fluoroanilino)-7-methoxy-6-(4-morpholinyl)-3-quinolin- ecarbonitrile .Iaddend.or a pharmaceutically acceptable salt thereof; ddd) 7-[3-(4-Benzyl-piperazin-1-yl)-propoxy]-4-(2,4-dichloro-5-methoxy-phenyla- mino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; eee) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-[3-(2-hydroxy-ethylamino)-propox- y]-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; fff) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-{3-[ethyl-(2-hydroxy-ethyl)-amin- o]-propoxy}-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ggg) 7-{3-[Bis-(2-methoxy-ethyl)-amino]-propoxy}-4-(2,4-dichloro-5-methoxy-phe- nylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; hhh) 7-{3-[Bis-(2-hydroxy-ethyl)-amino]-propoxy}-4-(2,4-dichloro-5-methoxy-phe- nylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; iii) 4-(3-chloro-4-fluoroanilino)-7-(4-morpholinyl)-6-nitro-3-quinolinecarboni- trile or a pharmaceutically acceptable salt thereof; jjj) N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-(4-morpholinyl)-6-quinolinyl]-2- -butynamide or a pharmaceutically acceptable salt thereof; kkk) 6-amino-4-(3-chloro-4-fluoroanilino)-7-(4-morpholinyl)-3-quinolinecarboni- trile or a pharmaceutically acceptable salt thereof; lll) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-(3-{[2-(4-morpholinyl)ethyl- ]amino}propoxy)-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; mmm) 7-{3-[(2-anilinoethyl)amino]propoxy}-4-(2,4-dichloro-5-methoxyanilino)-6-- methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; nnn) N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-(4-morpholinyl)-6-quinolinyl]ac- rylamide or a pharmaceutically acceptable salt thereof; ooo) 4-(3-chloro-4-fluoroanilino)-7-{4-[2-(dimethylamino)ethyl]-1-piperazinyl}- -6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ppp) 6-amino-4-(3-chloro-4-fluoroanilino)-7-{4-[2-(dimethylamino)ethyl]-1-pipe- razinyl}-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; qqq) N-(4-(3-chloro-4-fluoroanilino)-3-cyano-7-{4-[2-(dimethylamino)ethyl]-1-p- iperazinyl}-6-quinolinyl) acrylamide or a pharmaceutically acceptable salt thereof; rrr) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-({2-[4-(2-methoxyethyl)-1-p- iperazinyl]ethyl}amino)-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; sss) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(2H-1,2,3-triazol-2-yl)p- ropoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ttt) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(1H-1,2,3-triazol-1-yl)p- ropoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; uuu) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-(3-thienyl)-3-quinolinecarb- onitrile or a pharmaceutically acceptable salt thereof; vvv) 4-[(E)-2-(2-quinolinyl)ethenyl]aniline or a pharmaceutically acceptable salt thereof; www) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-{[2-(2H-1,2,3-triazol-2-yl)- ethyl]amino}-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; xxx) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-{[2-(1H-1,2,3-triazol-1-yl)- ethyl]amino}-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; yyy) 4-(2,4-dichloro-5-methoxyanilino)-7-(3-thienyl)-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; zzz) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(1H,1,2,4-triazol-1-yl)p- ropoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; aaaa) 4-(2,4-dichloro-5-methoxyanilino)-7-[3-(1H-imidazol-1-yl)propoxy]-6-metho- xy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; bbbb) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(1H-pyrazol-1-yl)p- ropoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; cccc) N-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-quinolinyl]-N-[4- -ethyl-1-piperazinyl) butyl]acetamide or a pharmaceutically acceptable salt thereof; dddd) N-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-quinolinyl]-N-(3- -(4-ethyl-1-piperazinyl)propyl)acetamide or a pharmaceutically acceptable

salt thereof; eeee) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-{3-[4-(2-methoxyethyl)-1-pi- perazinyl]propoxy}-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ffff) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-(1H-pyrrol-1-yl)-3-quinolin- ecarbonitrile or a pharmaceutically acceptable salt thereof; gggg) 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]- -3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; hhhh) 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-[2-(2H-1,2,3-triazol-2-yl)e- thoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; iiii) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(1H-tetraazol-1-yl)propo- xy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; jjjj) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(2H-tetraazol-2-yl- )propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; kkkk) 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]- -3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; llll) 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-[2-(2H-1,2,3-triazol-2-yl)e- thoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; or mmmm) 4-(2,4-dichloro-5-methoxyanilino)-7-{3-[[2-(dimethylamino)ethyl](methyl)a- mino]propoxy}-6-methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof.

.[.6. A method of treating, inhibiting the growth of, or eradicating a neoplasm in a mammal in need thereof which comprises administering to said mammal an effective amount of a compound of Formula 1 having the structure ##STR00055## wherein: X is cycloalkyl of 3 to 7 carbon atoms, which may be optionally substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a pyridinyl, pyrimidinyl, or phenyl ring wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalky of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, methylmercapto, and benzoylamino; Z is --NH--, --O--, --S--, or --NR--; R is alkyl of 1-6 carbon atoms, or carboalkyl of 2-7 carbon atoms; G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR00056## R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.k--Y--, R.sub.7--(C(R.sub.6).sub.2).sub.g--Y--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.p--M--(C(R.s- ub.6).sub.2).sub.k--Y--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.k--Y-- with the proviso that either G.sub.1 or G.sub.2 or both G.sub.1 and G.sub.2 must be a radical selected from the group ##STR00057## R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.k--Y--, R'.sub.7--(C(R.sub.6).sub.2).sub.g--Y--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.k--Y--, Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.k--Y--, or ##STR00058## Y is a divalent radical selected from the group consisting of ##STR00059## R.sub.7 is --NR.sub.6R.sub.6, -J, --OR.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6(OR.sub.6); R'.sub.7 is --NR.sub.6(OR.sub.6), --N(R.sub.6).sub.3.sup.+, alkenoxy of 1-6 carbon atoms, alkynoxy of 1-6 carbon atoms, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, N-alkyl-N-alkynylamino of 4 to 12 carbon atoms, N-alkenyl-N-alkynylamino of 4 to 12 carbon atoms, or N,N-dialkynylamino of 6-12 carbon atoms with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.pNR.sub.6R.sub.6, or >N--(C(R.sub.6).sub.2).sub.p--OR.sub.6; W is >NR.sub.6, --O-- or is a bond; Het is a heterocycle selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, pyridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, thiazole, thiazolidine, tetrazole, piperazine, furan, thiophene, tetrahydrothiophene, tetrahydrofuran, dioxane, 1,3-dioxolane, tetrahydropyran, and ##STR00060## wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.sOR.sub.6 or --(C(R.sub.6).sub.2).sub.sN(R.sub.6).sub.2, or optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.sO--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; R.sub.2, is selected from the group consisting of ##STR00061## ##STR00062## R.sub.3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR00063## R.sub.7--(C(R.sub.6).sub.2).sub.s--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.r--, R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.r--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r--; with the proviso that at least one of the R.sub.3 groups is selected from the group ##STR00064## R'.sub.7--(C(R.sub.6).sub.2).sub.s--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.r--, R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.r--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r--; with the proviso that for said at least one R.sub.3 group the moiety Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r-- cannot be morpholino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, piperidino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, N-alkyl piperidino-N-alkyl wherein either alkyl group is 1-6 carbon atoms, or azacycloalkyl-N-alkyl of 3-11 carbon atoms; R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR00065## R.sub.7--(C(R.sub.6).sub.2).sub.s--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.r--, R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.r--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r--; R.sub.8, and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.rNR.sub.6R.sub.6, or --(C(R.sub.6).sub.2).sub.rOR.sub.6; J is independently hydrogen, chlorine, fluorine, or bromine; Q is alkyl of 1-6 carbon atoms or hydrogen; a=0 or 1; g=1-6; k=0-4; n is 0-1; p=2-4; q=0-4; r=1-4; s=1-6; u 0-4 and v=0-4, wherein the sum of u+v is 2-4; or a pharmaceutically acceptable salt thereof, provided that when R.sub.6 is alkenyl of 2-7 carbon atoms or alkynyl of 2-7 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6-- and R.sub.7 is --NR.sub.6R.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6(OR.sub.6), then g=2-6; when M is --O-- and R.sub.7 is -OR.sub.6, then p=1-4; when Y is --NR.sub.6--, then k=2-4; when Y is --O-- and M or W is --O--, then k=1-4; when W is not a bond with Het bonded through a nitrogen atom, then q=2-4; and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6--, then k=2-4..].

.[.7. The method according to claim 6 wherein the neoplasm is selected from the group consisting of breast, kidney, bladder, mouth, larynx, esophagus, stomach, colon, ovary, and lung..].

.[.8. A method of treating, inhibiting the progression of, or eradicating polycystic kidney disease in a mammal in need thereof which comprises administering to said mammal an effective amount of a compound of formula 1 having the structure ##STR00066## wherein: X is cycloalkyl of 3 to 7 carbon atoms, which may be optionally substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a pyridinyl, pyrimidinyl, or phenyl ring wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalky of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, methylmercapto, and benzoylamino; Z is --NH--, --O--, --S--, or --NR--; R is alkyl of 1-6 carbon atoms, or carboalkyl of 2-7 carbon atoms; G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR00067## R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.k--Y--, R.sub.7--(C(R.sub.6).sub.2).sub.g--Y--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.k--Y--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.k--Y-- with the proviso that either G.sub.1 or G.sub.2 or both G.sub.1 and G.sub.2 must be a radical selected from the group ##STR00068## R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.k--Y--, R'.sub.7--(C(R.sub.6).sub.2).sub.g--Y--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.k--Y--, Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.k--Y--, or R.sub.2--N.sup.H--; Y is a divalent radical selected from the group consisting of ##STR00069## R.sub.7 is --NR.sub.6R.sub.6, --J, --OR.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6(OR.sub.6), R'.sub.7 is --NR.sub.6(OR.sub.6), --N(R.sub.6).sub.3.sup.+, alkenoxy of 1-6 carbon atoms, alkynoxy of 1-6 carbon atoms, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, N-alkyl-N-alkynylamino of 4 to 12 carbon atoms, N-alkenyl-N-alkynylamino of 4 to 12 carbon atoms, or N,N-dialkynylamino of 6-12 carbon atoms with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.pNR.sub.6R.sub.6, or >N--(C(R.sub.6).sub.2).sub.p--OR.sub.6; W is >NR.sub.6, --O-- or is a bond; Het is a heterocycle selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, pyridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, thiazole, thiazolidine, tetrazole, piperazine, furan, thiophene, tetrahydrothiophene, tetrahydrofuran, dioxane, 1,3-dioxolane, tetrahydropyran, and ##STR00070## wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.sOR.sub.6 or --(C(R.sub.6).sub.2).sub.sN(R.sub.6).sub.2, or optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.sO--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; R.sub.2, is selected from the group consisting of ##STR00071## ##STR00072## R.sub.3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR00073## R.sub.7--(C(R.sub.6).sub.2).sub.s--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.r--, R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.r--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r--; with the proviso that at least one of the R.sub.3 groups is selected from the group ##STR00074## R'.sub.7--(C(R.sub.6).sub.2).sub.s--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.r--, R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.r--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r--; with the proviso that for said at least one R.sub.3 group the moiety Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r-- cannot be morpholino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, piperidino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, N-alkyl piperidino-N-alkyl wherein either alkyl group is 1-6 carbon atoms, or azacycloalkyl-N-alkyl of 3-11 carbon atoms; R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR00075## R.sub.7--(C(R.sub.6).sub.2).sub.s--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.r--, R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.r--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r--; R.sub.8, and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.rNR.sub.6R.sub.6, or --(C(R.sub.6).sub.2).sub.rOR.sub.6; J is independently hydrogen, chlorine, fluorine, or bromine; Q is alkyl of 1-6 carbon atoms or hydrogen; a=0 or 1; g=1-6; k=0-4; n is 0-1; p=2-4; q=0-4; r=1-4; s=1-6; u=0-4 and v=0-4, wherein the sum of u+v is 2-4; or a pharmaceutically acceptable salt thereof, provided that when R.sub.6 is alkenyl of 2-7 carbon atoms or alkynyl of 2-7 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6-- and R.sub.7 is --NR.sub.6R.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6(OR.sub.6), then g=2-6; when M is --O-- and R.sub.7 is --OR.sub.6, then p=1-4; when Y is --NR.sub.6--, then k=2-4; when Y is --O-- and M or W is --O--, then k=1-4; when W is not a bond with Het bonded through a nitrogen atom, then q=2-4; and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6--, then k=2-4..].

.[.9. A pharmaceutical composition which comprises a compound of formula 1 having the structure ##STR00076## wherein: X is cycloalkyl of 3 to 7 carbon atoms, which may be optionally substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a pyridinyl, pyrimidinyl, or phenyl ring wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalky of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, methylmercapto, and benzoylamino; Z is --NH--, --O--, --S--, or --NR--; R is alkyl of 1-6 carbon atoms, or carboalkyl of 2-7 carbon atoms; G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR00077## R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.k--Y--, R.sub.7--(C(R.sub.6).sub.2).sub.g--Y--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.k--Y--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.k--Y-- with the proviso that either G.sub.1 or G.sub.2 or both G.sub.1 and G.sub.2 must be a radical selected from the group ##STR00078## R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.k--Y--, R'.sub.7--(C(R.sub.6).sub.2).sub.g--Y--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.k--Y--, Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.k--Y--, or ##STR00079## Y is a divalent radical selected from the group consisting of ##STR00080## R.sub.7 is --NR.sub.6R.sub.6, -J, --OR.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6(OR.sub.6); R'.sub.7 is --NR.sub.6(OR.sub.6), --N(R.sub.6).sub.3.sup.+, alkenoxy of 1-6 carbon atoms, alkynoxy of 1-6 carbon atoms, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, N-alkyl-N-alkynylamino of 4 to 12 carbon atoms, N-alkenyl-N-alkynylamino of 4 to 12 carbon atoms, or N,N-dialkynylamino of 6-12 carbon atoms with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.pNR.sub.6R.sub.6, or >N--(C(R.sub.6).sub.2).sub.p--OR.sub.6, W is >NR.sub.6, --O-- or is a bond; Het is a heterocycle selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, pyridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, thiazole, thiazolidine, tetrazole, piperazine, furan, thiophene, tetrahydrothiophene, tetrahydrofuran, dioxane, 1,3-dioxolane, tetrahydropyran, and ##STR00081## wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.sOR.sub.6 or --(C(R.sub.6).sub.2).sub.sN(R.sub.6).sub.2, or optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.sO--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; R.sub.2, is selected from the group consisting of ##STR00082## ##STR00083## R.sub.3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR00084## R.sub.7--(C(R.sub.6).sub.2).sub.s--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.r--, R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.r--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r--; with the proviso that at least one of the R.sub.3 groups is selected from the group ##STR00085## R'.sub.7--(C(R.sub.6).sub.2).sub.s--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.r--, R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.r--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r--; with the proviso that for said at least one R.sub.3 group the moiety Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r-- cannot be morpholino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, piperidino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, N-alkyl piperidino-N-alkyl wherein either alkyl group is 1-6 carbon atoms, or azacycloalkyl-N-alkyl of 3-11 carbon atoms; R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR00086## R.sub.7--(C(R.sub.6).sub.2).sub.s--, R.sub.7--(C(R.sub.6).sub.2).sub.p--M--(C(R.sub.6).sub.2).sub.r--, R.sub.8R.sub.9--CH--M--(C(R.sub.6).sub.2).sub.r--, or Het-(C(R.sub.6).sub.2).sub.q--W--(C(R.sub.6).sub.2).sub.r--; R.sub.8, and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.rNR.sub.6R.sub.6, or --(C(R.sub.6).sub.2).sub.rOR.sub.6; J is independently hydrogen, chlorine, fluorine, or bromine; Q is alkyl of 1-6 carbon atoms or hydrogen; a=0 or 1; g=1-6; k=0-4; n is 0-1; p=2-4; q=0-4; r=1-4; s=1-6; u=0-4 and v=0-4, wherein the sum of u+v is 2-4; or a pharmaceutically acceptable salt thereof, provided that when R.sub.6 is alkenyl of 2-7 carbon atoms or alkynyl of 2-7 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6-- and R.sub.7 is --NR.sub.6R.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6(OR.sub.6), then g=2-6; when M is --O-- and R.sub.7 is -OR.sub.6, then p=1-4; when Y is --NR.sub.6--, then k=2-4; when Y is --O-- and M or W is --O--, then k=1-4; when W is not a bond with Het bonded through a nitrogen atom, then q=2-4; and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6--, then k=2-4..].

.Iadd.10. A compound having the structure: ##STR00087## wherein: X is a phenyl ring, optionally mono-, di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalkyl of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, and benzoylamino; Z is --NH--; R.sub.1 and R.sub.4 are each hydrogen; G.sub.1 is hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR00088## Y is a divalent radical selected from the group consisting of ##STR00089## R.sub.7 is --NR.sub.6R.sub.6, --J, --OR.sub.6, --N(R.sub.6).sub.3.sup..+-., or --NR.sub.6(OR.sub.6); M is --N(R.sub.6)--, --O--, --N[(C(R.sub.6).sub.2).sub.pNR.sub.6R.sub.6]--, or --N[(C(R.sub.6).sub.2).sub.p--OR.sub.6]--; W is --N(R.sub.6)--, --O--, or is a bond; Het is a heterocycle selected from the group consisting of pyridine, 2,6-disubstituted morpholine, 2,5-disubstituted thiomorpholine, 2-substituted imidazole, substituted thiazole, thiazolidine, N-substituted imidazole, N-substituted 1,4-piperazine, N-substituted piperidine, dioxane, 1,3-dioxolane, and N-substituted pyrrolidine, wherein the heterocycle is optionally mono-or di-substituted on carbon or nitrogen with R.sub.6, optionally mono-or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono-or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.sOR.sub.6 or --(C(R.sub.6).sub.2).sub.sN(R.sub.6).sub.2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.sO--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; R.sub.8 and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.rNR.sub.6R.sub.6, or --(C(R.sub.6).sub.2).sub.rOR.sub.6; J is independently hydrogen, chlorine, fluorine, or bromine; a=0 or 1; g=1-6; k=0-4; n is 0; p=2-4; q=0-4; r=1-4; and s=1-6; or a pharmaceutically acceptable salt thereof, provided that when R.sub.6 is alkenyl of 2-6 carbon atoms or alkynyl of 2-6 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6-- and R.sub.7 is --NR.sub.6R.sub.6, --N(R.sub.6).sub.3.sup..+-., or --NR.sub.6(OR.sub.6), then g=2-6; when M is --O-- and R.sub.7 is --OR.sub.6, then p=1-4; when Y is --NR.sub.6--, then k=2-4; when Y is --O-- and M or W is --O--, then k=1-4; when W is not a bond with Het bonded through a nitrogen atom, then q=2-4; and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6--, then k=2-4..Iaddend.

.Iadd.11. A compound having the structure: ##STR00090## wherein: X is a phenyl ring, optionally mono-, di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalkyl of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, and benzoylamino; Z is --NH--; R.sub.1 and R.sub.4 are each hydrogen; G.sub.1 is hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR00091## Y is a divalent radical selected from the group consisting of ##STR00092## R.sub.7 is --NR.sub.6R.sub.6, --J, --OR.sub.6, --N(R.sub.6).sub.3.sup..+-., or --NR.sub.6(OR.sub.6); M is --N(R.sub.6)--, --O--, --N[(C(R.sub.6).sub.2).sub.pNR.sub.6R.sub.6]--, or --N[(C(R.sub.6).sub.2).sub.p--OR.sub.6]--; W is --N(R.sub.6)--, --O--, or is a bond; Het is N-substituted 1,4-piperazine; wherein Het is optionally mono-or di-substituted on carbon or nitrogen with R.sub.6, optionally mono-or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono-or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.sOR.sub.6 or --(C(R.sub.6).sub.2).sub.sN(R.sub.6).sub.2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.sO--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; R.sub.8 and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.rNR.sub.6R.sub.6, or --(C(R.sub.6).sub.2).sub.rOR.sub.6; J is independently hydrogen, chlorine, fluorine, or bromine; a=0 or 1; g=1-6; k=0-4; n is 0; p=2-4; q=0-4; r=1-4; and s=1-6; or a pharmaceutically acceptable salt thereof, provided that when R.sub.6 is alkenyl of 2-6 carbon atoms or alkynyl of 2-6 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6-- and R.sub.7 is --NR.sub.6R.sub.6, --N(R.sub.6).sub.3.sup..+-., or --NR.sub.6(OR.sub.6), then g=2-6; when M is --O-- and R.sub.7 is --OR.sub.6, then p=1-4; when Y is --NR.sub.6--, then k=2-4; when Y is --O-- and M or W is --O--, then k=1-4; when W is not a bond with Het bonded through a nitrogen atom, then q=2-4; and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6--, then k=2-4..Iaddend.

.Iadd.12. A compound having the structure: ##STR00093## wherein: X is a phenyl ring tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalkyl of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, and benzoylamino; Z is --NH--; R.sub.1 and R.sub.4 are each hydrogen; G.sub.1 is hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR00094## Y is a divalent radical selected from the group consisting of ##STR00095## R.sub.7 is --NR.sub.6R.sub.6, --J, --OR.sub.6, --N(R.sub.6).sub.3.sup..+-., or --NR.sub.6(OR.sub.6); M is --M(R.sub.6)--, --O--, --N[(C(R.sub.6).sub.2).sub.pNR.sub.6R.sub.6]--, or N[(C(R.sub.6).sub.2).sub.p--OR.sub.6]--; W is --N(R.sub.6)--, --O--, or is a bond; Het is a heterocycle selected from the group consisting of pyridine, 2,6-disubstituted morpholine, 2,5-disubstituted thiomorpholine, 2-substituted imidazole, substituted thiazole, thiazolidine, N-substituted imidazole, N-substituted 1,4-piperazine, N-substituted piperidine, dioxane, 1,3-dioxolane, and N-substituted pyrrolidine; wherein the heterocycle is optionally mono-or di-substituted on carbon or nitrogen with R.sub.6, optionally mono-or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono-or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.sOR.sub.6 or --(C(R.sub.6).sub.2).sub.sN(R.sub.6).sub.2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.sO--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; R.sub.8 and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.rNR.sub.6R.sub.6, or --(C(R.sub.6).sub.2).sub.rOR.sub.6; J is independently hydrogen, chlorine, fluorine, or bromine; a=0 or 1; g=1-6; k=0-4; n is 0; p=2-4; q=0-4; r=1-4; and s=1-6; or a pharmaceutically acceptable salt thereof, provided that when R.sub.6 is alkenyl of 2-6 carbon atoms or alkynyl of 2-6 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6-- and R.sub.7 is --NR.sub.6R.sub.6, --N(R.sub.6).sub.3.sup..+-., or --NR.sub.6(OR.sub.6), then g=2-6; when M is --O-- and R.sub.7 is --OR.sub.6, then p=1-4; when Y is --NR.sub.6--, then k=2-4; when Y is --O-- and M or W is --O--, then k=1-4; when W is not a bond with Het bonded through a nitrogen atom, then q=2-4; and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6--, then k=2-4..Iaddend.

.Iadd.13. The compound according to claim 12, wherein Het is N-substituted 1,4-piperazine, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.14. A compound having the structure: ##STR00096## wherein: X is a phenyl ring optionally mono-, di-, or tri-substituted with a halogen; Z is --NH--; R.sub.1 and R.sub.4 are each hydrogen; G.sub.1 is hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR00097## Y is a divalent radical selected from the group consisting of ##STR00098## R.sub.7 is --NR.sub.6R.sub.6, --J, --OR.sub.6, --N(R.sub.6).sub.3.sup..+-., or --NR.sub.6(OR.sub.6); M is --N(R.sub.6)--, --O--, --N[(C(R.sub.6).sub.2).sub.pNR.sub.6R.sub.6]--, or --N[(C(R.sub.6).sub.2).sub.p--OR.sub.6]--; W is --N(R.sub.6)--, --O--, or is a bond; Het is a heterocycle selected from the group consisting of pyridine, 2,6-disubstituted morpholine, 2,5-disubstituted thiomorpholine, 2-substituted imidazole, substituted thiazole, thiazolidine, N-substituted imidazole, N-substituted 1,4-piperazine, N-substituted piperidine, dioxane, 1,3-dioxolane, and N-substituted pyrrolidine; wherein the heterocycle is optionally mono-or di-substituted on carbon or nitrogen with R.sub.6, optionally mono-or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono-or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.sOR.sub.6 or --(C(R.sub.6).sub.2).sub.sN(R.sub.6).sub.2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.sO--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; R.sub.8 and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.rNR.sub.6R.sub.6, or --(C(R.sub.6).sub.2).sub.rOR.sub.6; J is independently hydrogen, chlorine, fluorine, or bromine; a=0 or 1; g=1-6; k=0-4; n is 0; p=2-4; q=0-4; r=1-4; and s=1-6; or a pharmaceutically acceptable salt thereof, provided that when R.sub.6 is alkenyl of 2-6 carbon atoms or alkynyl of 2-6 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6-- and R.sub.7 is --NR.sub.6R.sub.6, --N(R.sub.6).sub.3.sup..+-., or --NR.sub.6(OR.sub.6), then g=2-6; when M is --O-- and R.sub.7 is --OR.sub.6, then p=1-4; when Y is --NR.sub.6--, then k=2-4; when Y is --O-- and M or W is --O--, then k=1-4; when W is not a bond with Het bonded through a nitrogen atom, then q=2-4; and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6--, then k=2-4..Iaddend.

.Iadd.15. The compound according to claim 14, wherein X is a phenyl ring optionally mono-, di-, or tri-substituted with chloro, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.16. The compound according to claim 14, wherein Het is N-substituted 1,4-piperazine, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.17. A compound having the structure: ##STR00099## wherein: X is a phenyl ring optionally mono-, di-, or tri-substituted with an alkoxy of 1-6 carbons; Z is --NH--; R.sub.1 and R.sub.4 are each hydrogen; G.sub.1 is hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR00100## Y is a divalent radical selected from the group consisting of ##STR00101## R.sub.7 is --NR.sub.6R.sub.6, --J, --OR.sub.6, --N(R.sub.6).sub.3.sup..+-., or --NR.sub.6(OR.sub.6); M is --N(R.sub.6)--, --O--, --N[(C(R.sub.6).sub.2).sub.pNR.sub.6R.sub.6]--, or --N[(C(R.sub.6).sub.2).sub.p--OR.sub.6]--; W is --N(R.sub.6)--, --O-- or is a bond; Het is a heterocycle selected from the group consisting of pyridine, 2,6-disubstituted morpholine, 2,5-disubstituted thiomorpholine, 2-substituted imidazole, substituted thiazole, thiazolidine, N-substituted imidazole, N-substituted 1,4-piperazine, N-substituted piperidine, dioxane, 1,3-dioxolane, and N-substituted pyrrolidine; wherein the heterocycle is optionally mono-or di-substituted on carbon or nitrogen with R.sub.6, optionally mono-or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono-or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.sOR.sub.6 or --(C(R.sub.6).sub.2).sub.sN(R.sub.6).sub.2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.sO--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; R.sub.8 and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.rNR.sub.6R.sub.6, or --(C(R.sub.6).sub.2).sub.rOR.sub.6; J is independently hydrogen, chlorine, fluorine, or bromine; a=0 or 1; g=1-6; k=0-4; n is 0; p=2-4; q=0-4; r=1-4; and s=1-6; or a pharmaceutically acceptable salt thereof, provided that when R.sub.6 is alkenyl of 2-6 carbon atoms or alkynyl of 2-6 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6-- and R.sub.7 is --NR.sub.6R.sub.6, --N(R.sub.6).sub.3.sup..+-., or --NR.sub.6(OR.sub.6), then g=2-6; when M is --O-- and R.sub.7 is --OR.sub.6, then p=1-4; when Y is --NR.sub.6--, then k=2-4; when Y is --O-- and M or W is --O--, then k=1-4; when W is not a bond with Het bonded through a nitrogen atom, then q=2-4; and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6--, then k=2-4..Iaddend.

.Iadd.18. The compound according to claim 17, wherein X is a phenyl ring optionally mono-, di-, or tri-substituted with methoxy, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.19. The compound according to claim 17, wherein Het is N-substituted 1,4-piperazine, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.20. A compound having the structure: ##STR00102## wherein: X is a phenyl ring, optionally mono-, di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalkyl of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, and benzoylamino; Z is --NH--; R.sub.1 and R.sub.4 are each hydrogen; G.sub.1 is hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR00103## Y is a divalent radical selected from the group consisting of ##STR00104## R.sub.7 is --NR.sub.6R.sub.6, --J, --OR.sub.6, --N(R.sub.6).sub.3.sup..+-., or --NR.sub.6(OR.sub.6); M is --N(R.sub.6)--, --O--, --N[(C(R.sub.6).sub.2).sub.pNR.sub.6R.sub.6]--, or --N[(C(R.sub.6).sub.2).sub.p--OR.sub.6]--; W is --N(R.sub.6)--, --O--, or is a bond; Het is a piperazine optionally mono-or di-substituted on carbon or nitrogen with R.sub.6, optionally mono-or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono-or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.sOR.sub.6 or --(C(R.sub.6).sub.2).sub.sN(R.sub.6).sub.2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.sO--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; R.sub.8 and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.rNR.sub.6R.sub.6, or --(C(R.sub.6).sub.2).sub.rOR.sub.6; J is independently hydrogen, chlorine, fluorine, or bromine; a=0 or 1; g=1-6; k=0-4; n is 0; p=2-4; q=0-4; r=1-4; and s=1-6; or a pharmaceutically acceptable salt thereof, provided that when R.sub.6 is alkenyl of 2-6 carbon atoms or alkynyl of 2-6 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6-- and R.sub.7 is --NR.sub.6R.sub.6, --N(R.sub.6).sub.3.sup..+-., or --NR.sub.6(OR.sub.6), then g=2-6; when M is --O-- and R.sub.7 is --OR.sub.6, then p=1-4; when Y is --NR.sub.6--, then k=2-4; when Y is --O-- and M or W is --O--, then k=1-4; when W is not a bond with Het bonded through a nitrogen atom, then q=2-4; and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6--, then k=2-4..Iaddend.

.Iadd.21. The compound according to claim 20, wherein X is a tri-substituted phenyl ring, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.22. The compound according to claim 20, wherein X is a phenyl ring optionally mono-, di-, or tri-substituted with a halogen, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.23. The compound according to claim 22, wherein X is a phenyl ring optionally mono-, di-, or tri-substituted with chloro, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.24. The compound according to claim 20, wherein X is a phenyl ring optionally mono-, di-, or tri-substituted with an alkoxy of 1-6 carbons, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.25. The compound according to claim 24, wherein X is a phenyl ring optionally mono-, di-, or tri-substituted with methoxy, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.26. The compound according to claim 20, wherein G.sub.1 is alkoxy of 1-6 carbons, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.27. The compound according to claim 26, wherein G.sub.1 is methoxy, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.28. A compound having the structure: ##STR00105## wherein: X is a phenyl ring, optionally mono-, di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalkyl of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, and benzoylamino; Z is --NH--; R.sub.1 and R.sub.4 are each hydrogen; G.sub.1 is alkoxy of 1-6 carbons; W is --N(R.sub.6)--, --O--, or is a bond; Het is a heterocycle selected from the group consisting of pyridine, 2,6-disubstituted morpholine, 2,5-disubstituted thiomorpholine, 2-substituted imidazole, substituted thiazole, thiazolidine, N-substituted imidazole, N-substituted 1,4-piperazine, N-substituted piperidine, dioxane, 1,3-dioxolane, and N-substituted pyrrolidine; wherein the heterocycle is optionally mono-or di-substituted on carbon or nitrogen with R.sub.6, optionally mono-or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono-or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.sOR.sub.6 or --(C(R.sub.6).sub.2).sub.sN(R.sub.6).sub.2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.sO--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; k=0-4; n is 0; and s=1-6; or a pharmaceutically acceptable salt thereof, provided that when R.sub.6 is alkenyl of 2-6 carbon atoms or alkynyl of 2-6 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom..Iaddend.

.Iadd.29. The compound according to claim 28, wherein Het is N-substituted 1,4-piperazine, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.30. The compound according to claim 29, wherein X is a tri-substituted phenyl ring, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.31. The compound according to claim 29, wherein X is a phenyl ring optionally mono-, di-, or tri-substituted with a halogen, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.32. The compound according to claim 31, wherein X is a phenyl ring optionally mono-, di-, or tri-substituted with chloro, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.33. The compound according to claim 29, wherein X is a phenyl ring optionally mono-, di-, or tri-substituted with an alkoxy of 1-6 carbons, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.34. The compound according to claim 33, wherein X is a phenyl ring optionally mono-, di-, or tri-substituted with methoxy, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.35. The compound according to any one of claims 28 to 34, wherein G.sub.1 is methoxy, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.36. The compound according to any one of claims 10 to 34, wherein W is a bond, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.37. The compound according to any one of claims 10 to 34, wherein W is a bond, Het is bonded through a nitrogen atom, and k is 2 to 4, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.38. The compound according to any one of claims 10 to 34, wherein k is 3, or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.39. A pharmaceutical composition which comprises a compound of any one of claim 5 or 10-34 or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.40. A pharmaceutical composition which comprises a compound of claim 35 or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.41. A pharmaceutical composition which comprises a compound of claim 36 or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.42. A pharmaceutical composition which comprises a compound of claim 37 or a pharmaceutically acceptable salt thereof..Iaddend.

.Iadd.43. A pharmaceutical composition which comprises a compound of claim 38 or a pharmaceutically acceptable salt thereof..Iaddend.
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