Claims for Patent: 6,288,082

Summary for Patent: 6,288,082

Title:	Substituted 3-cyanoquinolines
Abstract:	This invention provides compounds of formula I having the structurewherein 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, Mark E. Salvati, Philip Frost
Assignee:	Wyeth Holdings LLC
Application Number:	US09/406,573
Patent Claims:	1. A compound of formula 1 having the structure: wherein: X is a bicyclic aryl or bicyclic heteroaryl ring system of 8 to 12 atoms where the bicyclic heteroaryl ring contains 1 to 4 heteroatoms selected from N, O, and S with the proviso that the bicyclic heteroaryl ring does not contain O—O, S—S, or S—O bonds and where the bicyclic aryl or bicyclic heteroaryl ring may be optionally mono- di-, tri, or tetra-substituted with a substituent selected from the group consisting of halogen, oxo, thio, 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, dialkyl amino 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, and benzoylamino; or X is a radical having the formula: wherein A is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- or di-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, alkylamnino 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, and benzoylamino; T is bonded to a carbon of A and is: —NH(CH2)m—, —O(CH2)m—, —S(CH2)m—, —NR(CH2)m—, —(CH2)m— —(CH2)mNH—, —(CH2)mO—, —(CH2)mS—, or —(CH2)mNR—; L is an unsubsitituted phenyl ring or a phenyl ring 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, and benzoylamino; provided that L can be an unsubstituted phenyl ring only when m>0 and T is not —CH2NH— or —CH2O—; or L is a 5- or 6-membered heteroaryl ring where the heteroaryl ring contains 1 to 3 heteroatoms selected from N, O, and S, with the proviso that the heteroaryl ring does not contain O—O, S—S, or S—O bonds, and where the heteroaryl ring is optionally mono- or di-substituted with a substituent selected from the group consisting of halogen, oxo, thio, 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, 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, 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—Y—; or R1 and R4 are as defined above and G1 or G2 or both are R2—NH—; or if any of the substituents R1, G2, G3, or R4 are located on contiguous carbon atoms then they may be taken together as the divalent radical —O—C(R6)2—O—; Y is a divalent radical selected from the group consisting of R7 is —NR6R6, —OR6, —J, —N(R6)3 +, or —NR6(OR6); 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 is 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 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, and 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; with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; 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—; 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; m is 0-3; 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 substituted or unsubstituted bicyclic aryl or bicyclic heteroaryl ring system, or a pharmaceutically acceptable salt thereof. 4. The compound according to claim 2 wherein X is the radical: and A is a phenyl ring, or a pharmaceutically acceptable salt thereof. 5. The compound according to claim 3 wherein R1 and R4 are hydrogen or a pharmaceutically acceptable salt thereof. 6. The compound according to claim 4 wherein R1 and R4 are hydrogen or a pharmaceutically acceptable salt thereof. 7. The compound according to claim 3 wherein the bicyclic aryl or bicyclic heteroaryl ring system is selected from the group consisting of naphthaline, 1,2,3,4-tetrahydronaphthaline, indane, 1-oxo-indane, 1,2,3,4-tetrahydroquinoline, naphthyridine, benzofuran, 3-oxo-1,3-dihydro-isobenzofuran, benzothiaphene, 1,1-dioxo-benzothiaphene, indole, 2,3-dihydroindole, 1,3-dioxo-2,3-dihydro-1H-isoindole, benzotriazole, 1H-indazole, indoline, benzopyrazole, 1,3-benzodioxole, benzooxazole, purine, phthalimide, coumarin, chromone, quinoline, terahydroquinoline, isoquinoline, benzimidazole, quinazoline, pyrido[2,3-b]pyridine, pyrido[3,4-b]pyrazine, pyrido[3,2-c]pyridazine, pyrido[3,4-b]pyridine, 1H-pyrazole[3,4-d]pyrimidine, 1,4-Benzodioxane, pteridine, 2(1H)-quinolone, 1(2H)-isoquinolone, 2-oxo-2,3-dihydro-benzthiazole, 1,2-methylenedioxybenzene, 2-oxindole, 1,4-benzisoxazine, benzothiazole, quinoxaline, quinoline-N-oxide, isoquinoline-N-oxide, quinoxaline-N-oxide, quinazoline-N-oxide, benzoazine, phthalazine, 1,4-dioxo-1,2,3,4-tetrahydro-phthalazine, 2-oxo-1,2-dihydro-quinoline, 2,4-dioxo-1,4-dihydro-2H-benzo[d][1,3]oxazine, 2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine, and cinnoline or a pharmaceutically acceptable salt thereof. 8. The compound according to claim 4 wherein L is 5 or 6-membered heteroaryl ring or a pharmaceutically acceptable salt thereof. 9. The compound according to claim 8 wherein the heteroaryl ring is selected from the group consisting of pyridine, pyrimidine, imidazole, thiazole, thiazolidine, pyrrole, furan, thiophene, oxazole, and 1,2,4-triazole or a pharmaceutically acceptable salt thereof. 10. The compound according to claim 4 wherein L is a substituted phenyl ring or a pharmaceutically acceptable salt thereof. 11. The compound according to claim 1, which is: a) 4-(2,3-dihydro-1H-indol-6-ylamino)-6,7-diethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; b) 4-(benzothiazol-6-ylamino)-6,7-diethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; c) 4-(benzo[1,3]dioxol-5-ylamino)-6,7-diethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; d) 6,7-diethoxy-4-(1H-indazol-6-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; e) 6,7-diethoxy-4-(4-methyl-2-oxo-2H-chromen-7-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; f) 6,7-diethoxy-4-(1H-indol-6-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; g) 6,7-dimethoxy-4-(1H-indazol-6-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; h) 4-(1,3-dioxo-2,3-dihydro-1H-isoindol-5-ylamino)-6,7-diethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; i) 4-(2,3-dihydro-benzo[1,4]dioxin-6-ylamino)-6,7-diethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; j) 4-(1H-indazol-6-ylamino)-6,7-bis-(2-methoxy-ethoxy)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; k) 4-(1,4-dioxo-1,2,3,4-tetrahydro-phthalazin-6-ylamino)-6,7-diethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; l) 6,7-diethoxy-4-(indan-5-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; m) 4-(2,4-dioxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-ylamino)-6,7-diethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; n) 6,7-diethoxy-4-(3-oxo-1,3-dihydro-isobenzofuran-5-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; o) 4-(1,1-dioxo-1H-benzo[b]thiophen-6-ylamino)-6,7-diethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; p) 4-(2,3-dihydro-1H-indol-6-ylamino)-6,7-dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; q) 7-ethoxy-4-(indazol-6-ylamino)-6-methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; r) 4-(2,3-dihydro-1H-indol-6-ylamino)-6-methoxy-7-(3-pyridin-4-yl-propoxy)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; s) 9-(1H-indazol-6-ylamino)-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carbonitrile or a pharmaceutically acceptable salt thereof; t) 6,7-diethoxy-4-(1-methyl-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-7-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; u) 4-(1H-indazol-6-ylamino)-6,7,8-trimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; v) 6,7-dimethoxy-4-(4-methyl-2-oxo-1,2-dihydro-quinolin-7-ylamino)-quinoline-3-carbonitrile w) 6,7-dimethoxy-4-(2-methyl-benzothiazol-5-ylamino)-quinoline-3-carbonitrile x) 6,7-dimethoxy-4-(2-oxo-2,3-dihydro-benzothiazol-6-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; y) 6,7-dimethoxy-4-(quinolin-5-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; z) 4-(isoquinolin-5-ylamino)-6,7-dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; aa) 6,7-dimethoxy-4-(quinolin-8-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; bb) 4-(8-hydroxy-quinolin-5-ylamino)-6,7-dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; cc) 4-(1H-indol-4-ylamino)-6,7-dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; dd) 4-(1H-indazol-5-ylamino)-6,7-dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ee) 4-(1H-Indazol-6-ylamino)-5,8-dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ff) 4-(1H-indazol-6-ylamino)-7-methoxy-6-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; gg) 4-(3H-benzotriazol-5-ylamino)-7-methoxy-6-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; hh) 4-(1H-indazol 6-ylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ii) 4-(3H-benzotriazol-5-ylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; jj) 4-(1H-indazol-6-ylamino)-7-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; kk) 4-(3H-benzotriazol-5-ylamino)-7-methoxy-quinoline-3-carbinitile or a pharmaceutically acceptable salt thereof; ll) 7-hydroxy-4-(1H-indazol-6-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; mm) 4-(1H-indol-5-ylamino)-7-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; nn) 7-hydroxy-4-(3H-benzotrizol-5-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; oo) 4-(1H-indazol-6-ylamino)-8-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; pp) 4-(3H-benzotriazol-5-ylamino)-8-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; qq) 4-(1H-indol-5-ylamino)-6,7-Dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; rr) 4-(1H-benzoimidazol-5-ylamino)-6,7-dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ss) 6,7-dimethoxy-4-(2-methyl-1H-benzoimidazol-5-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; tt) 6,7-dimethoxy-4-(quinoline-6-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; uu) 4-(4-chloro-naphthalen-1-ylamino)-6,7-Dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; vv) 6,7-dimethoxy-4-(5,6,7,8,-tetrahydro-naphthalen-1-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ww) 4-(3H-benzotriazol-5-ylamino)-6,7,8-Trimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; xx) 4-(1H-indazol -6-ylamino)-6-methoxy-7-[2-(4-methyl-piperazin-1-yl)-ethoxy]-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; yy) 7-{2-[(2-hydroxy-ethyl)-amino]-ethoxy}-4(1H-indazol-6-ylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; zz) 7-{2-[bis-(2-hydroxy-ethyl)-amino]-ethoxy}-4-(1H-indazol-6-ylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; aaa) 7-[2-(4-hydroxy-piperidin-1-yl)-ethoxy]-4-(-indazol-6-ylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; bbb) 7-{2-[(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethoxy]-4-(1H-indazol-6-ylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ccc) 7-[2-(1,4dioxa-8-aza-spiro[4,5]dec-8-yl)-ethoxy]-4-(1H-indazol-6 -ylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ddd) 7-[2-([1,3]dioxolan-2-ylmethyl-methyl-amino)-ethoxy]-4-(1H-indazol-6-ylamino)-6-methoxy-quinoline-3-carbonitrile eee) 7-[2-(3,4-dihydro-1H-isoquinolin-2-yl)-ethoxy]-4-(1H-indazol-6-ylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; fff) 4-(1H-indazol-6-ylamino)-6-methoxy-7-(2-thiomorpholin-4-yl-ethoxy)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ggg) 7-(2-chloroethoxy)-4-(1H-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; hhh) 7-(2-dimethylaminoethoxy)-4-(1H-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; iii) 4-(1H-indazol-6-ylamino)-6-methoxy-7-(2-morpholin-4-yl-ethoxy)quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; jjj) 4-(3H-benzotriazol-5-ylamino)-7-(2-chloroethoxy)-6-methoxyquinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; kkk) 7-(3-chloropropoxy)-4-(1H-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; lll) 4-(1H-indazole-6-ylamino)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; mmm) 4-[3-chloro-4-(1-methyl-2-imidazolylthio)phenylamino]-6,7-diethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; nnn) 4-[3-chloro-4-(1-methyl-2-imidazolylthio)phenylamino]-6,7-dimethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ooo) 6-amino-4-[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)-phenylamino]-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ppp) N-{4-[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)-phenylamino]-3-cyano-quinolin-6-yl}-acrylamide or a pharmaceutically acceptable salt thereof; qqq) 6-amino-4-(1H-indol-5-ylamino)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; rrr) 4-(1H-indol-5-ylamino)-6-nitro-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; sss) 4-(2-Hydroxy-naphthalen-1-ylamino)-6,7-dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ttt) 4-(2,3-Dihydro-benzo[1,4]dioxin-6-ylamino)-6,7-dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; uuu) 4-(2-Mercapto-benzothiazol-6-ylamino)-6,7-dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; vvv) 4-(6-Hydroxy-naphthalen-1-ylamino)-6,7-dimethoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; www) 4-(1H-Indazol-6-ylamino)-5-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; xxx) 4-(2-chloro-5-methoxyanilino)-5-methoxyquinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; yyy) 4-[(2-Amino-4-chlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; zzz) 4-[(3-hydroxy-2-naphthyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; aaaa) 4-{3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]anilino}-7-methoxy-6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; bbbb) 6-amino-4-{3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]anilino}-7-methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; cccc) (E)-N-(4-{3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]anilino}-3-cyano-7-methoxy-6-quinolinyl)-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; dddd) 4-[3-chloro-4-(1,3-thiazol-2-ylsulfanyl)anilino]-7-methoxy-6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; eeee) 6-amino-4-[3-chloro-4-(1,3-thiazol-2-ylsulfanyl)anilino]-7-methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ffff) (E)-N-{4-[3-chloro-4-(1,3-thiazol-2-ylsulfanyl)anilino]-3-cyano-7-methoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; gggg) 4-[3-chloro-4-(1H-imidazol-1-yl)anilino]-7-methoxy-6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; hhhh) 6-amino-4-[3-chloro-4-(1H-imidazol-1-yl)anilino]-7-methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; iiii) (E)-N-{4-[3-chloro-4-(1H-imidazol-1-yl)anilino]-3-cyano-7-methoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; jjjj) 4-{3-chloro-4[(4-oxo-3,4-dihydro-2-quinazolinyl)sulfanyl]anilino}-7-methoxy-6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; kkkk) 6-amino-4-3-chloro-4-[(4-oxo-3,4-dihydro-2-quinazolinyl)sulfanyl]anilino)-7-methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; llll) (E)-N-(4-{3-chloro-4-[(4-oxo-3,4-dihydro-2-quinazolinyl)sulfanyl]anilino}-3-cyano-7-methoxy-6-quinolinyl)-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; mmmm) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(4-pyridinylmethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; nnnn) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(3-pyridinylmethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; oooo) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(2-pyridinylmethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; pppp) (E)-N-(4-{4-[acetyl(3-pyridinylmethyl)amino]-3-chloroanilino}-3-cyano-7-methoxy-6-quinolinyl)-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; qqqq) N-(2-chloro-4-[(3-cyano-7-methoxy-6-nitro-4-quinolinyl)amino]phenyl}-N-(3-pyridinylmethyl)acetamide or a pharmaceutically acceptable salt thereof; rrrr) N-{4-[(6-amino-3-cyano-7-methoxy-4-quinolinyl)amino]-2-chlorophenyl}-N-(3-pyridinylmethyl)acetamide or a pharmaceutically acceptable salt thereof; ssss) N-(4-{[6-(acetylamino)-3-cyano-7-methoxy-4-quinolinyl]amino}-2-chlorophenyl)-N-(3-pyridinylmethyl)acetamide or a pharmaceutically acceptable salt thereof; tttt) 4-[3-chloro-4-(1,3-dimethyl-2,4,6-trioxohexahydro-5-pyrimidinyl)anilino]-7-methoxy-6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; uuuu) 4-{3-chloro-4-[(4-phenyl-1,3-thiazol-2-yl)sulfanyl]anilino}-7-methoxy-6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; vvvv) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(3-thienylmethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; wwww) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(2-thienylmethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; xxxx) 6-methoxy-4-(4-phenoxyanilino)-7-[2-(2H-1,2,3-triazol-2-yl)ethoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; yyyy) 6-methoxy-4-(4-phenoxyanilino)-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; zzzz) 4-(4-benzylanilino)-6-methoxy-7-[2-(2H-1,2,3-triazol-2-yl)ethoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; aaaaa) 4-(4-benzylanilino)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; bbbbb) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(2-pyridinyloxy)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ccccc) 4-{3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]anilino}-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ddddd) 4-[4-(2-furylmethyl)anilino]-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; eeeee) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(tetrahydro-2-furanylmethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; fffff) 4-[4-(3-furylmethyl)anilino]-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ggggg) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(tetrahydro-3-furanylmethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; hhhhh) 4-(3-chloro-4-{[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]amino}anilino)-7-ethoxy-6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; iiiii) (E)-N-[4-(3-chloro-4-{[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]amino}anilino)-3-cyano-7-ethoxy-6-quinolinyl]-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; jjjjj) 4-[3-chloro-4-(4-pyridinyloxy)anilino]-7-ethoxy-6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; kkkkk) 6-amino-4-[3-chloro-4-(4-pyridinyloxy)anilino]-7-ethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; lllll) (E)-N-{4-[3-chloro-4-(4-pyridinyloxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; mmmmm) 4-{3-chloro-4-[(3-pyridinylmethyl)amino]anilino}-7-methoxy-6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; nnnnn) 6-amino-4-{3-chloro-4-[(4-phenyl-1,3-thiazol-2-yl)sulfanyl]anilino}-7-methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ooooo) 6-amino-4-(3-chloro-4-{[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]amino}anilino)-7-ethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ppppp) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(2-phenylethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; qqqqq) (E)-N-(4-{3-chloro-4-[(4-phenyl-1,3-thiazol-2-yl)sulfanyl]anilino}-3-cyano-7-methoxy-6-quinolinyl)-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; rrrrr) 4-[3-chloro-4-(1H-imidazol-1-yl)anilino]-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; sssss) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(3-pyridinyloxy)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ttttt) 4-[3-chloro-4-(4-pyridinyloxy)anilino]-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; uuuuu) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(4-pyridinyloxy)anilinol-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; vvvvv) 4-[2-chloro-4-(1,3-thiazol-2-ylsulfanyl)anilino]-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; wwwww) N-[2-chloro-4-({3-cyano-6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl}amino)phenyl]-N-(3-pyridinylmethyl)acetamide or a pharmaceutically acceptable salt thereof; xxxxx) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(1H-tetraazol-5-ylmethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; yyyyy) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(2H-1,2,3-triazol-2-ylmethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; zzzzz) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(1H-1,2,3-triazol-1-ylmethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; aaaaaa) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[2-(2H-1,2,3-triazol-2-yl)ethoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; bbbbbb) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; cccccc) 7-ethoxy-6-nitro-4-[4-[(4-phenyl-1,3-thiazol-2-yl)sulfanyl]-3-(trifluoromethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; dddddd) 6-amino-7-ethoxy-4-[4-[(4-phenyl-1,3-thiazol-2-yl)sulfanyl]-3-(trifluoromethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; eeeeee) (E)-N-{3-cyano-7-ethoxy-4-[4-[(4-phenyl-1,3-thiazol-2-yl)sulfanyl]-3-(trifluoromethyl)anilino]-6-quinolinyl}-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; ffffff) 4-[3-chloro-4-(1H-imidazol-1-ylmethyl)anilino]-7-ethoxy-6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; gggggg) 6-amino-4-[3-chloro-4-(1H-imidazol-1-ylmethyl)anilino]-7-ethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; hhhhhh) (E)-N-{4-[3-chloro-4-(1H-imidazol-1-ylmethyl)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; iiiiii) 4-{3-chloro-4-[(4-methyl-2-pyrimidinyl)sulfanyl]anilino}-7-ethoxy-6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; jjjjjj) 6-amino-4-{3-chloro-4-[(4-methyl-2-pyrimidinyl)sulfanyl]anilino}-7-ethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; kkkkkk) (E)-N-(4-{3-chloro-4-[(4-methyl-2-pyrimidinyl)sulfanyl]anilino}-3-cyano-7-ethoxy-6-quinolinyl)-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; llllll) 4-{3-chloro-4-[(4,6-dimethyl-2-pyrimidinyl)sulfanyl]anilino}-7-ethoxy-6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; mmmmmm) 6-amino-4-{3-chloro-4-[(4,6-dimethyl-2-pyrimidinyl)sulfanyl]anilino}-7-ethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; nnnnnn) (E)-N-(4-{3-chloro-4-[(4,6-dimethyl-2-pyrimidinyl)sulfanyl]anilino}-3-cyano-7-ethoxy-6-quinolinyl)-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; oooooo) 4-[4-(1H-imidazol-2-ylmethyl)anilino]-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; pppppp) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(1H-tetraazol-1-ylmethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; qqqqqq) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(2H-tetraazol-2-ylmethyl)anilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; rrrrrr) 4-{3-chloro-4-[(4,6-dimethyl-2-pyrimidinyl)sulfanyl]anilino}-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ssssss) 4-{3-chloro-4-[(4-methyl-2-pyrimidinyl)sulfanyl]anilino}-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; tttttt) (E)-N-[4-(3-chloro-4-{[2-(phenylsulfanyl)acetyl]amino}anilino)-3-cyano-7-methoxy-6-quinolinyl]-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; uuuuuu) 4-[4-(2,6-dimethoxyphenoxy)anilino]-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; vvvvvv) 6-methoxy-4-[4-(3-methoxyphenoxy)anilino]-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; wwwwww) 6-methoxy-4-{4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]anilino}-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; xxxxxx) (E)-N-{4-[3-chloro-4-(1,3-thiazol-2-ylsulfanyl)anilino]-3-cyano-7-methoxy-6-quinolinyl}-4-[(2-methoxyethyl)(methyl)amino]-2-butenamide or a pharmaceutically acceptable salt thereof; yyyyyy) (E)-N-(4-{3-chloro-4-[(5-phenyl-1,3-thiazol-2-yl)sulfanyl]anilino}-3-cyano-7-methoxy-6-quinolinyl)-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; zzzzzz) (E)-N-(4-{3-chloro-4-[(4-phenyl-1,3-thiazol-2-yl)sulfanyl]anilino}-3-cyano-7-′ethoxy-6-quinolinyl)-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; aaaaaaa) 4-{3-chloro-4-[(4,6-dimethyl-2-pyrimidinyl)sulfanyl]anilino}-6,7-dimethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; bbbbbbb) 6,7-dimethoxy-4-({6-[(4-phenyl-1,3-thiazol-2-yl)sulfanyl]-3-pyridinyl}amino)-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; or ccccccc) 4-{3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]anilino}-6-methoxy-7-[3-(1H-1,2,3-triazol-1-yl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof. 12. A method of treating, inhibiting the growth of, or eradicating neoplasms 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 a bicyclic aryl or bicyclic heteroaryl ring system of 8 to 12 atoms where the bicyclic heteroaryl ring contains 1 to 4 heteroatoms selected from N, O, and S with the proviso that the bicyclic heteroaryl ring does not contain O—O, S—S, or S—O bonds and where the bicyclic aryl or bicyclic heteroaryl ring may be optionally mono- di-, tri, or tetra-substituted with a substituent selected from the group consisting of halogen, oxo, thio, 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, and benzoylamino; or X is a radical having the formula: wherein A is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- or di-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, and benzoylamino; T is bonded to a carbon of A and is: —NH(CH2)m—, —O(CH2)m—, —S(CH2)m—, —NR(CH2)m—, —(CH2)m— —(CH2)mNH—, —(CH2)mO—, —(CH2)mS—, or —(CH2)mNR—; L is an unsubsitituted phenyl ring or a phenyl ring 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-alkyliminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, and benzoylamino; provided that L can be an unsubstituted phenyl ring only when m>0 and T is not —CH2NH— or —CH2O—; or L is a 5- or 6-membered heteroaryl ring where the heteroaryl ring contains 1 to 3 heteroatoms selected from N, O, and S, with the proviso that the heteroaryl ring does not contain O—O, S—S, or S—O bonds, and where the heteroaryl ring is optionally mono- or di-substituted with a substituent selected from the group consisting of halogen, oxo, thio, 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, 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 oi 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, 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—; or R1 and R4 are as defined above and G1 or G2 or both are R2—NH—; or if any of the substituents R1, G2, G3, or R4 are located on contiguous carbon atoms then they may be taken together as the divalent radical —O—C(R6)2—O—; Y is a divalent radical selected from the group consisting of R7 is —NR6R6, —OR6, —J, —N(R6)3 +, or —NR6(OR6); 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 is 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 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, and 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; with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; 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—; 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; m is 0-3; 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. 13. The method according to claim 12 wherein the neoplasm is selected from the group consisting of breast, kidney, bladder, mouth, larynx, esophagus, stomach, colon, ovary, and lung. 14. 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 a bicyclic aryl or bicyclic heteroaryl ring system of 8 to 12 atoms where the bicyclic heteroaryl ring contains 1 to 4 heteroatoms selected from N, O, and S with the proviso that the bicyclic heteroaryl ring does not contain O—O, S—S, or S—O bonds and where the bicyclic aryl or bicyclic heteroaryl ring may be optionally mono- di-, tri, or tetra-substituted with a substituent selected from the group consisting of halogen, oxo, thio, 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, and benzoylamino; or X is a radical having the formula: wherein A is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- or di-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, and benzoylamino; T is bonded to a carbon of A and is: —NH(CH2)m—, —O(CH2)m—, —S(CH2)m—, —NR(CH2)m—, —(CH2)m— —(CH2)mNH—, —(CH2)mO—, —(CH2)mS—, or —(CH2)mNR—; L is an unsubsitituted phenyl ring or a phenyl ring 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, and benzoylamino; provided that L can be an unsubstituted phenyl ring only when m>0 and T is not —CH2NH— or —CH2O—; or L is a 5- or 6-membered heteroaryl ring where the heteroaryl ring contains 1 to 3 heteroatoms selected from N, O, and S, with the proviso that the heteroaryl ring does not contain O—O, S—S, or S—O bonds, and where the heteroaryl ring is optionally mono- or di-substituted with a substituent selected from the group consisting of halogen, oxo, thio, 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, 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, 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—; or R1 and R4 are as defined above and G1 or G2 or both are R2—NH—; or if any of the substituents R1, G2, G3, or R4 are located on contiguous carbon atoms then they may be taken together as the divalent radical —O—C(R6)2—O—; Y is a divalent radical selected from the group consisting of R7 is —NR6R6, —OR6, —J, —N(R6)3 +, or —NR6(OR6); 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 is 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 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, and 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; with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; 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—; 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; m is 0-3; 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. 15. A pharmaceutical composition which comprises a compound of formula 1 having the structure wherein: X is a bicyclic aryl or bicyclic heteroaryl ring system of 8 to 12 atoms where the bicyclic heteroaryl ring contains 1 to 4 heteroatoms selected from N, O, and S with the proviso that the bicyclic heteroaryl ring does not contain O—O, S—S, or S—O bonds and where the bicyclic aryl or bicyclic heteroaryl ring may be optionally mono- di-, tri, or tetra-substituted with a substituent selected from the group consisting of halogen, oxo, thio, 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, and benzoylamino; or X is a radical having the formula: wherein A is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- or di-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, and benzoylamino; T is bonded to a carbon of A and is: —NH(CH2)m—, —O(CH2)m—, —S(CH2)m—, —NR(CH2)m—, —(CH2)m— —(CH2)mNH—, —(CH2)mO—, —(CH2)mS—, or —(CH2)mNR—; L is an unsubsitituted phenyl ring or a phenyl ring 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, allkylthio 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, and benzoylamino; provided that L can be an unsubstituted phenyl ring only when m>0 and T is not —CH2NH— or —CH2O—; or L is a 5- or 6-membered heteroaryl ring where the heteroaryl ring contains 1 to 3 heteroatoms selected from N, O, and S, with the proviso that the heteroaryl ring does not contain O—O, S—S, or S—O bonds, and where the heteroaryl ring is optionally mono- or di-substituted with a substituent selected from the group consisting of halogen, oxo, thio, 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, 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, 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—; or R1 and R4 are as defined above and G1 or G2 or both are R2—NH—; or if any of the substituents R1, G2, G3, or R4 are located on contiguous carbon atoms then they may be taken together as the divalent radical —O—C(R6)2—O—; Y is a divalent radical selected from the group consisting of R7 is —NR6R6, —OR6, —J, —N(R6)3 +, or —NR6(OR6); 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 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 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, and 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; with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; 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—; 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; m is 0-3; 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 and a pharmaceutical carrier.