Claims for Patent: RE42376

Summary for Patent: RE42376

Title:	Substituted 3-cyanoquinolines
Abstract:	This invention provides compounds of formula I having the structure wherein G1, G2, R1, R4, 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):	Allan Wissner, Hwei-Ru Tsou, Dan M. Berger, Middleton B. Floyd, Jr., Philip R. Hamann, Nan Zhang, Philip Frost
Assignee:	Wyeth Holdings LLC
Application Number:	US12/785,269
Patent Claims:	1. A compound of Formula 1 having the structure: 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; G1, G2, R1, and R4 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, R8R9—CH—M—(C(R6)2)k—Y—, R7—(C(R6)2)g—Y—, R7—(C(R6)2)pM—(C(R6)2)k—Y—, or Het-(C(R6)2)q—W—(C(R6)2)k—Y— with the proviso that either G1 or G2 or both G1 and G2 must be a radical selected from the group R8R9—CH—M—(C(R6)2)k—Y—, R′7—C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)k—Y—, Het-(C(R6)2)q—W—(C(R6)2)k—Y—, or Y is a divalent radical selected from the group consisting of R7 is —NR6R6, —J, —OR6, —N(R6)3 +, or —NR6(OR6); R′7 is —N(OR6), —N(R6)3 +, 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 >NR6, —O—, >N—(C(R6)2)pNR6R6, or >N—(C(R6)2)p—OR6; W is >NR6, —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 wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R6, optionally mono- or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono or di-substituted on carbon with the mono-valent radicals —(C(R6)2)SOR6 or —(C(R6)2)SN(R6)2, or optionally mono or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)SO—; R6 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; R2, is selected from the group consisting of R3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r, or Het-(C(R6)2)q—W—(C(R6)2)r—; with the proviso that at least one of the R3 groups is selected from the group R′7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—; with the proviso that for said at least one R3 group the moiety Het-(C(R6)2)q—W—(C(R6)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; R5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—; R8, and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6; 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 R6 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 —NR6— and R7 is —NR6R6, —N(R6)3 +, or —NR6(OR6), then g 2-6; when M is —O— and R7 is —OR6, then p=1-4; when Y is —NR6—, 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 —NR6—, 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 R1 and R4 are hydrogen or a pharmaceutically acceptable salt thereof. 5. The A 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-methylamino)-2-butynamide or a pharmaceutically acceptable salt thereof; c) N-[4-[(3-Bromophenyl)amino]-3-cyano-6-quinolinyl]-4-(N-methoxyethyl-N-methylamino)-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-quinoline-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 4-((2S)-2-Methoxymethylpyrrolidin-1-yl)but-2-ynoic acid[4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]-amide 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 4-(1,4-Dioxa-8-azaspiro[4,5]dec-8-yl)but-2-ynoic acid[4-(3-Bromophenylamino)-3-cyanoquinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; j) 4-(3-Bromo-phenylamino)-6-(2-ethoxy-3,4-dioxo-cyclobut-1-enylamino)-quinoline-3-carbonitrile 4-(3-Bromo-phenylamino)-6-[(2-ethoxy-3,4-dioxo-cyclobut-1-enyl]amino)-quinoline-3-carbonitrile 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 4-[(2-Methoxyethyl)(methyl)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; 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]-amide 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]-amide 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]-amide or a pharmaceutically acceptable salt thereof; q) 4-(3-hydroxy-4-methyl-phenylamino)-6-methoxy-7-(3-pyridin-4-yl-propoxy)-quinoline-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]-amide 4-Diallylamino-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide 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]-amide 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 4-[([1,3]Dioxolan-2-yl-methyl)(methyl)amino]-but-2-enoic acid[3-cyano-7-methoxy-quinolin-6-yl]-amide 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]-amide 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]-amide 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]-amide 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]-amide 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]-amide 4-[(Methoxy)(methyl)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; z) 4-(4-Hydroxy-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; aa) 4-[1,4′]Bipiperidinyl-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; bb) 4-Thiazolidin-3-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; cc) 3-{3-[4-(3-Chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-ylcarbamoyl]-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]-amide 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]-amide 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]-amide 4-[(2-Hydroxyethyl)(methyl)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; 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]-amide 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]-amide 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-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ll) 6-(1-Aziridinyl)-4-(3-chloro-4-fluoroanilino)-7-methoxy-3-quinolinecarbonitrile 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 4-[(2-Methoxyethyl)(methyl)amino]-but-2-enoic acid[4-(3-bromo-phenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; nn) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-[3-(4-hydroxy-piperidin-1-yl)-propoxy]-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)-piperazin-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 4-(2-Bromo-4-chloro-phenylamino)-7-{2-[(2-hydroxyethyl)(methyl)amino]-ethoxy}-6-methoxy-quinoline-3-carbonitrile 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 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-{3-[(2-hydroxyethyl)(methyl)amino]-propoxy}-6-methoxy-quinoline-3-carbonitrile 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-ethylamino)-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)-propoxy]-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-quinolin-7-yloxy]-propyl}-piperidine-4-carboxylic acid ethyl ester 1-{3-[3-Cyano-4-(2,4-dichloro-5-methoxy-phenylamino)-6-methoxy-quinolin-7-yl-oxy]-propyl}-piperidine-4-carboxylic acid ethyl ester or a pharmaceutically acceptable salt thereof; bbb) 7-[3-(4-acetyl-1-piperazinyl)propoxy]-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ccc) 4-(3-chloro-4-fluoroanilino)-7-methyoxy-6(4-morpholinyl)-3-quinolinecarbonitrile 4-(3-Chloro-4-fluoroanilino)-7-methoxy-6-(4-morpholinyl)-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ddd) 7-[3-(4-Benzyl-piperazin-1-yl)-propoxy]-4-(2,4-dichloro-5-methoxy-phenylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; eee) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-[3-(2-hydroxy-ethylamino)-propoxy]-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)-amino]-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-phenylamino)-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-phenylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; iii) 4-(3-chloro-4-fluoroanilino)-7-(4-morpholinyl)-6-nitro-3-quinolinecarbonitrile 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-quinolinecarbonitrile 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]acrylamide 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-piperazinyl}-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; qqq) N-(4-(3-chloro-4-fluoroanilino)-3-cyano-7-{4-[2-(dimethylamino)ethyl]-1-piperazinyl}-6-quinolinyl) acrylamide or a pharmaceutically acceptable salt thereof; rrr) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-({2-[4-(2-methoxyethyl)-1-piperazinyl]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)propoxy]-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)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; uuu) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-(3-thienyl)-3-quinolinecarbonitrile 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)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; aaaa) 4-(2,4-dichloro-5-methoxyanilino)-7-[3-(1H-imidazol-1-yl)propoxy]-6-methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; bbbb) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(1H-pyrazol-1-yl)propoxy]-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-piperazinyl]propoxy}-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ffff) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-(1H-pyrrol-1-yl)-3-quinolinecarbonitrile 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)ethoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; iiii) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(1H-tetraazol-1-yl)propoxy]-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)ethoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; or mmmm) 4-(2,4-dichloro-5-methoxyanilino)-7-{3-[[2-(dimethylamino)ethyl](methyl)amino]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 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; G1, G2, R1, and R4 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, R8R9—CH—M—(C(R6)2)k—Y—, R7—(C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)p—M—(C(R6)2)k—Y—, or Het-(C(R6)2)q—W—(C(R6)2)k—Y— with the proviso that either G1 or G2 or both G1 and G2 must be a radical selected from the group R8R9—CH—M—(C(R6)2)k—Y—, R′7—(C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)k—Y—, Het-(C(R6)2)q—W—(C(R6)2)k—Y—, or Y is a divalent radical selected from the group consisting of R7 is —NR6R6, -J, —OR6, —N(R6)3 +, or —NR6(OR6); R′7 is —NR6(OR6), —N(R6)3 +, 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 >NR6, —O—, >N—(C(R6)2)pNR6R6, or >N—(C(R6)2)p—OR6; W is >NR6, —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 wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R6, optionally mono- or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—; R6 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; R2, is selected from the group consisting of R3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—; with the proviso that at least one of the R3 groups is selected from the group R′7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—; with the proviso that for said at least one R3 group the moiety Het-(C(R6)2)q—W—(C(R6)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; R5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—; R8, and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6; 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 R6 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 —NR6— and R7 is —NR6R6, —N(R6)3 +, or —NR6(OR6), then g=2-6; when M is —O— and R7 is -OR6, then p=1-4; when Y is —NR6—, 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 —NR6—, 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 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; G1, G2, R1, and R4 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, R8R9—CH—M—(C(R6)2)k—Y—, R7—(C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)k—Y—, or Het-(C(R6)2)q—W—(C(R6)2)k—Y— with the proviso that either G1 or G2 or both G1 and G2 must be a radical selected from the group R8R9—CH—M—(C(R6)2)k—Y—, R′7—(C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)k—Y—, Het-(C(R6)2)q—W—(C(R6)2)k—Y—, or R2—NH—; Y is a divalent radical selected from the group consisting of R7 is —NR6R6, —J, —OR6, —N(R6)3 +, or —NR6(OR6), R′7 is —NR6(OR6), —N(R6)3 +, 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 >NR6, —O—, >N—(C(R6)2)pNR6R6, or >N—(C(R6)2)p—OR6; W is >NR6, —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 wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R6, optionally mono- or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—; R6 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; R2, is selected from the group consisting of R3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—; with the proviso that at least one of the R3 groups is selected from the group R′7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—; with the proviso that for said at least one R3 group the moiety Het-(C(R6)2)q—W—(C(R6)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; R5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—; R8, and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6; 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 R6 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 —NR6— and R7 is —NR6R6, —N(R6)3 +, or —NR6(OR6), then g=2-6; when M is —O— and R7 is —OR6, then p=1-4; when Y is —NR6—, 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 —NR6—, then k=2-4. 9. A pharmaceutical composition which comprises a compound of formula 1 having the structure 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; G1, G2, R1, and R4 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, R8R9—CH—M—(C(R6)2)k—Y—, R7—(C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)k—Y—, or Het-(C(R6)2)q—W—(C(R6)2)k—Y— with the proviso that either G1 or G2 or both G1 and G2 must be a radical selected from the group R8R9—CH—M—(C(R6)2)k—Y—, R′7—(C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)k—Y—, Het-(C(R6)2)q—W—(C(R6)2)k—Y—, or Y is a divalent radical selected from the group consisting of R7 is —NR6R6, -J, —OR6, —N(R6)3 +, or —NR6(OR6); R′7 is —NR6(OR6), —N(R6)3 +, 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 >NR6, —O—, >N—(C(R6)2)pNR6R6, or >N—(C(R6)2)p—OR6, W is >NR6, —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 wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R6, optionally mono- or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—; R6 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; R2, is selected from the group consisting of R3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—; with the proviso that at least one of the R3 groups is selected from the group R′7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—; with the proviso that for said at least one R3 group the moiety Het-(C(R6)2)q—W—(C(R6)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; R5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—; R8, and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6; 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 R6 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 —NR6— and R7 is —NR6R6, —N(R6)3 +, or —NR6(OR6), then g=2-6; when M is —O— and R7 is -OR6, then p=1-4; when Y is —NR6—, 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 —NR6—, then k=2-4. 10. A compound having the structure: 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—; R1 and R4 are each hydrogen; G1 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, Y is a divalent radical selected from the group consisting of R7 is —NR6R6, —J, —OR6, —N(R6)3 ±, or —NR6(OR6); M is —N(R6)—, —O—, —N[(C(R6)2)pNR6R6]—, or —N[(C(R6)2)p—OR6]—; W is —N(R6)—, —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 R6, optionally mono-or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono-or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—; R6 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; R8 and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6; 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 R6 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 —NR6— and R7 is —NR6R6, —N(R6)3 ±, or —NR6(OR6), then g=2-6; when M is —O— and R7 is —OR6, then p=1-4; when Y is —NR6—, 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 —NR6—, then k=2-4. 11. A compound having the structure: 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—; R1 and R4 are each hydrogen; G1 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, Y is a divalent radical selected from the group consisting of R7 is —NR6R6, —J, —OR6, —N(R6)3 ±, or —NR6(OR6); M is —N(R6)—, —O—, —N[(C(R6)2)pNR6R6]—, or —N[(C(R6)2)p—OR6]—; W is —N(R6)—, —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 R6, optionally mono-or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono-or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—; R6 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; R8 and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6; 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 R6 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 —NR6— and R7 is —NR6R6, —N(R6)3 ±, or —NR6(OR6), then g=2-6; when M is —O— and R7 is —OR6, then p=1-4; when Y is —NR6—, 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 —NR6—, then k=2-4. 12. A compound having the structure: 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—; R1 and R4 are each hydrogen; G1 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, Y is a divalent radical selected from the group consisting of R7 is —NR6R6, —J, —OR6, —N(R6)3 ±, or —NR6(OR6); M is —M(R6)—, —O—, —N[(C(R6)2)pNR6R6]—, or N[(C(R6)2)p—OR6]—; W is —N(R6)—, —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 R6, optionally mono-or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono-or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—; R6 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; R8 and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6; 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 R6 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 —NR6— and R7 is —NR6R6, —N(R6)3 ±, or —NR6(OR6), then g=2-6; when M is —O— and R7 is —OR6, then p=1-4; when Y is —NR6—, 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 —NR6—, then k=2-4. 13. The compound according to claim 12, wherein Het is N-substituted 1,4-piperazine, or a pharmaceutically acceptable salt thereof. 14. A compound having the structure: wherein: X is a phenyl ring optionally mono-, di-, or tri-substituted with a halogen; Z is —NH—; R1 and R4 are each hydrogen; G1 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, Y is a divalent radical selected from the group consisting of R7 is —NR6R6, —J, —OR6, —N(R6)3 ±, or —NR6(OR6); M is —N(R6)—, —O—, —N[(C(R6)2)pNR6R6]—, or —N[(C(R6)2)p—OR6]—; W is —N(R6)—, —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 R6, optionally mono-or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono-or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—; R6 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; R8 and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6; 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 R6 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 —NR6— and R7 is —NR6R6, —N(R6)3 ±, or —NR6(OR6), then g=2-6; when M is —O— and R7 is —OR6, then p=1-4; when Y is —NR6—, 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 —NR6—, then k=2-4. 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. 16. The compound according to claim 14, wherein Het is N-substituted 1,4-piperazine, or a pharmaceutically acceptable salt thereof. 17. A compound having the structure: wherein: X is a phenyl ring optionally mono-, di-, or tri-substituted with an alkoxy of 1-6 carbons; Z is —NH—; R1 and R4 are each hydrogen; G1 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, Y is a divalent radical selected from the group consisting of R7 is —NR6R6, —J, —OR6, —N(R6)3 ±, or —NR6(OR6); M is —N(R6)—, —O—, —N[(C(R6)2)pNR6R6]—, or —N[(C(R6)2)p—OR6]—; W is —N(R6)—, —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 R6, optionally mono-or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono-or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—; R6 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; R8 and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6; 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 R6 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 —NR6— and R7 is —NR6R6, —N(R6)3 ±, or —NR6(OR6), then g=2-6; when M is —O— and R7 is —OR6, then p=1-4; when Y is —NR6—, 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 —NR6—, then k=2-4. 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. 19. The compound according to claim 17, wherein Het is N-substituted 1,4-piperazine, or a pharmaceutically acceptable salt thereof. 20. A compound having the structure: 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—; R1 and R4 are each hydrogen; G1 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, Y is a divalent radical selected from the group consisting of R7 is —NR6R6, —J, —OR6, —N(R6)3 ±, or —NR6(OR6); M is —N(R6)—, —O—, —N[(C(R6)2)pNR6R6]—, or —N[(C(R6)2)p—OR6]—; W is —N(R6)—, —O—, or is a bond; Het is a piperazine optionally mono-or di-substituted on carbon or nitrogen with R6, optionally mono-or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono-or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—; R6 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; R8 and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6; 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 R6 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 —NR6— and R7 is —NR6R6, —N(R6)3 ±, or —NR6(OR6), then g=2-6; when M is —O— and R7 is —OR6, then p=1-4; when Y is —NR6—, 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 —NR6—, then k=2-4. 21. The compound according to claim 20, wherein X is a tri-substituted phenyl ring, or a pharmaceutically acceptable salt thereof. 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. 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. 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. 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. 26. The compound according to claim 20, wherein G1 is alkoxy of 1-6 carbons, or a pharmaceutically acceptable salt thereof. 27. The compound according to claim 26, wherein G1 is methoxy, or a pharmaceutically acceptable salt thereof. 28. A compound having the structure: 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—; R1 and R4 are each hydrogen; G1 is alkoxy of 1-6 carbons; W is —N(R6)—, —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 R6, optionally mono-or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono-or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono-or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—; R6 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 R6 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. 29. The compound according to claim 28, wherein Het is N-substituted 1,4-piperazine, or a pharmaceutically acceptable salt thereof. 30. The compound according to claim 29, wherein X is a tri-substituted phenyl ring, or a pharmaceutically acceptable salt thereof. 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. 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. 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. 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. 35. The compound according to any one of claims 28 to 34, wherein G1 is methoxy, or a pharmaceutically acceptable salt thereof. 36. The compound according to any one of claims 10 to 34, wherein W is a bond, or a pharmaceutically acceptable salt thereof. 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. 38. The compound according to any one of claims 10 to 34, wherein k is 3, or a pharmaceutically acceptable salt thereof. 39. A pharmaceutical composition which comprises a compound of any one of claim 5 or 10-34 or a pharmaceutically acceptable salt thereof. 40. A pharmaceutical composition which comprises a compound of claim 35 or a pharmaceutically acceptable salt thereof. 41. A pharmaceutical composition which comprises a compound of claim 36 or a pharmaceutically acceptable salt thereof. 42. A pharmaceutical composition which comprises a compound of claim 37 or a pharmaceutically acceptable salt thereof. 43. A pharmaceutical composition which comprises a compound of claim 38 or a pharmaceutically acceptable salt thereof.