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 structure ##STR1## wherein G.sub.1, G.sub.2, R.sub.1, R.sub.4, Z, n, and X are defined in the specification or a pharmaceutically acceptable salt thereof which are useful as antineoplastic agents and in the treatment of polycystic kidney disease.
Inventor(s):	Wissner; Allan (Ardsley, NY), Tsou; Hwei-Ru (New City, NY), Berger; Dan M. (New City, NY), Floyd, Jr.; Middleton B. (Suffern, NY), Hamann; Philip R. (Gernerville, NY), Zhang; Nan (Eastchester, NY), Salvati; Mark E. (Lawrenceville, NJ), Frost; Philip (Morris Township, NJ)
Assignee:	American Cyanamid Company (Madison, NJ)
Application Number:	09/406,573
Patent Claims:	1. A compound of formula 1 having the structure: ##STR42## 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: ##STR43## 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(CH.sub.2).sub.m --, --O(CH.sub.2).sub.m --, --S(CH.sub.2).sub.m --, --NR(CH.sub.2).sub.m --, --(CH.sub.2).sub.m -- --(CH.sub.2).sub.m NH--, --(CH.sub.2).sub.m O--, --(CH.sub.2).sub.m S--, or --(CH.sub.2).sub.m NR--; 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 --CH.sub.2 NH-- or --CH.sub.2 O--; 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; G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR44## R.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2 --Y--; or R1 and R4 are as defined above and G.sub.1 or G.sub.2 or both are R.sub.2 --NH--; or if any of the substituents R.sub.1, G.sub.2, G.sub.3, or R.sub.4 are located on contiguous carbon atoms then they may be taken together as the divalent radical --O--C(R.sub.6).sub.2 --O--; Y is a divalent radical selected from the group consisting of ##STR45## R.sub.7 is --NR.sub.6 R.sub.6, --OR.sub.6, --J, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6); M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.p NR.sub.6 R.sub.6, or >N--(C(R.sub.6).sub.2).sub.p --OR.sub.6 ; W is >NR.sub.6, --O-- or is a bond; Het is 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 ##STR46## wherein Het is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.s OR.sub.6 or --(C(R.sub.6).sub.2).sub.s N(R.sub.6).sub.2, and optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.s O--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; R.sub.2, is selected from the group consisting of ##STR47## ##STR48## R.sub.3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR49## R.sub.7 --(C(R.sub.6).sub.2).sub.s --, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.r --, R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.r --, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r--; R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR50## R.sub.7 --(C(R.sub.6).sub.2).sub.s --, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.r --, R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.r --, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r --; R.sub.8, and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.r NR.sub.6 R.sub.6, or --(C(R.sub.6).sub.2).sub.r OR.sub.6 ; J is independently hydrogen, chlorine, fluorine, or bromine; Q is alkyl of 1-6 carbon atoms or hydrogen; a=0 or 1; g=1-6; k=0-4; n is 0-1; 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 R.sub.6 is alkenyl of 2-7 carbon atoms or alkynyl of 2-7 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6 -- and R.sub.7 is --NR.sub.6 R.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6), then g=2-6; when M is --O-- and R.sub.7 is --OR.sub.6 then p=1-4; when Y is --NR.sub.6 -- then k=2-4; when Y is --O-- and M or W is --O-- then k=1-4 when W is not a bond with Het bonded through a nitrogen atom then q=2-4 and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6 -- then k=2-4. 2. The compound according to claim 1 wherein Z is --NH-- and n=0 or a pharmaceutically acceptable salt thereof. 3. The compound according to claim 2 wherein X is 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: ##STR51## and A is a phenyl ring, or a pharmaceutically acceptable salt thereof. 5. The compound according to claim 3 wherein R.sub.1 and R.sub.4 are hydrogen or a pharmaceutically acceptable salt thereof. 6. The compound according to claim 4 wherein R.sub.1 and R.sub.4 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-carbonitr ile 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-c arbonitrile or a pharmaceutically acceptable salt thereof; i) 4-(2,3-dihydro-benzo[1,4]dioxin-6-ylamino)-6,7-diethoxy-quinoline-3-carbon itrile or a pharmaceutically acceptable salt thereof; j) 4-(1H-indazol-6-ylamino)-6,7-bis-(2-methoxy-ethoxy)-quinoline-3-carbonitri le or a pharmaceutically acceptable salt thereof; k) 4-(1,4-dioxo-1,2,3,4-tetrahydro-phthalazin-6-ylamino)-6,7-diethoxy-quinoli ne-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-qu inoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; n) 6,7-diethoxy-4-(3-oxo-1,3-dihydro-isobenzofuran-5-ylamino)-quinoline-3-car bonitrile or a pharmaceutically acceptable salt thereof; o) 4-(1,1-dioxo-1H-benzo[b]thiophen-6-ylamino)-6,7-diethoxy-quinoline-3-carbo nitrile 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)-qu inoline-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-carboni trile 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]diaz epin-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-car bonitrile 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)-quino line-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-carbonit rile 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-car bonitrile 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-c arbonitrile or a pharmaceutically acceptable salt thereof; yy) 7-{2-[(2-hydroxy-ethyl)-amino]-ethoxy}-4(1H-indazol-6-ylamino)-6-methoxy-q uinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; zz) 7-{2-[bis-(2-hydroxy-ethyl)-amino]-ethoxy}-4-(1H-indazol-6-ylamino)-6-meth oxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; aaa) 7-[2-(4-hydroxy-piperidin-1-yl)-ethoxy]-4-(-indazol-6-ylamino)-6-methoxy-q uinoline-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-ylami no)-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)-quinoli ne-3-carbonitrile or a pharmaceutically acceptable salt thereof; ggg) 7-(2-chloroethoxy)-4-(1H-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitr ile or a pharmaceutically acceptable salt thereof; hhh) 7-(2-dimethylaminoethoxy)-4-(1H-indazol-6-ylamino)-6-methoxyquinoline-3-ca rbonitrile 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-carb onitrile or a pharmaceutically acceptable salt thereof; kkk) 7-(3-chloropropoxy)-4-(1H-indazol-6-ylamino)-6-methoxyquinoline-3-carbonit rile 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-quino linecarbonitrile or a pharmaceutically acceptable salt thereof; nnn) 4-[3-chloro-4-(1-methyl-2-imidazolylthio)phenylamino]-6,7-dimethoxy-3-quin olinecarbonitrile or a pharmaceutically acceptable salt thereof; ooo) 6-amino-4-[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)-phenylamino]-qui noline-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-carbo nitrile or a pharmaceutically acceptable salt thereof; uuu) 4-(2-Mercapto-benzothiazol-6-ylamino)-6,7-dimethoxy-quinoline-3-carbonitri le 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-ni tro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; bbbb) 6-amino-4-{3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]anilino}-7-meth oxy-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-quino linecarbonitrile or a pharmaceutically acceptable salt thereof; eeee) 6-amino-4-[3-chloro-4-(1,3-thiazol-2-ylsulfanyl)anilino]-7-methoxy-3-quino linecarbonitrile 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-quinolinecarb onitrile or a pharmaceutically acceptable salt thereof; hhhh) 6-amino-4-[3-chloro-4-(1H-imidazol-1-yl)anilino]-7-methoxy-3-quinolinecarb onitrile or a pharmaceutically acceptable salt thereof; iiii) (E)-N-{4-[3-chloro-4-(1H-imidazol-1-yl)anilino]-3-cyano-7-methoxy-6-quinol inyl}-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-methox y-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-me thoxy-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-chloropheny l)-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-ni tro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; vvvv) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(3-thienylmethyl)anilino]-3-qu inolinecarbonitrile or a pharmaceutically acceptable salt thereof; wwww) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(2-thienylmethyl)anilino]-3-qu inolinecarbonitrile or a pharmaceutically acceptable salt thereof; xxxx) 6-methoxy-4-(4-phenoxyanilino)-7-[2-(2H-1,2,3-triazol-2-yl)ethoxy]-3-quino linecarbonitrile or a pharmaceutically acceptable salt thereof; yyyy) 6-methoxy-4-(4-phenoxyanilino)-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]-3-quino linecarbonitrile or a pharmaceutically acceptable salt thereof; zzzz) 4-(4-benzylanilino)-6-methoxy-7-[2-(2H-1,2,3-triazol-2-yl)ethoxy]-3-quinol inecarbonitrile or a pharmaceutically acceptable salt thereof; aaaaa) 4-(4-benzylanilino)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]-3-quinol inecarbonitrile or a pharmaceutically acceptable salt thereof; bbbbb) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(2-pyridinyloxy)anilino]-3-qui nolinecarbonitrile 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-quin olinecarbonitrile or a pharmaceutically acceptable salt thereof; eeeee) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(tetrahydro-2-furanylmethyl)an ilino]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; fffff) 4-[4-(3-furylmethyl)anilino]-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quin olinecarbonitrile or a pharmaceutically acceptable salt thereof; ggggg) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(tetrahydro-3-furanylmethyl)an ilino]-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}ani lino)-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-quinolinecarboni trile or a pharmaceutically acceptable salt thereof; kkkkk) 6-amino-4-[3-chloro-4-(4-pyridinyloxy)anilino]-7-ethoxy-3-quinolinecarboni trile or a pharmaceutically acceptable salt thereof; lllll) (E)-N-{4-[3-chloro-4-(4-pyridinyloxy)anilino]-3-cyano-7-ethoxy-6-quinoliny l}-4-(dimethylamino)-2-butenamide or a pharmaceutically acceptable salt thereof; mmmmm) 4-{3-chloro-4-[(3-pyridinylmethyl)amino]anilino}-7-methoxy-6-nitro-3-quino linecarbonitrile or a pharmaceutically acceptable salt thereof; nnnnn) 6-amino-4-{3-chloro-4-[(4-phenyl-1,3-thiazol-2-yl)sulfanyl]anilino}-7-meth oxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ooooo) 6-amino-4-(3-chloro-4-{[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]amino}an ilino)-7-ethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ppppp) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(2-phenylethyl)anilino]-3-quin olinecarbonitrile 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)pro poxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; sssss) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(3-pyridinyloxy)anilino]-3-qui nolinecarbonitrile or a pharmaceutically acceptable salt thereof; ttttt) 4-[3-chloro-4-(4-pyridinyloxy)anilino]-6-methoxy-7-[3-(4-morpholinyl)propo xy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; uuuuu) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(4-pyridinyloxy)anilinol-3-qui nolinecarbonitrile or a pharmaceutically acceptable salt thereof; vvvvv) 4-[2-chloro-4-(1,3-thiazol-2-ylsulfanyl)anilino]-6-methoxy-7-[3-(4-morphol inyl)propoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; wwwww) N-[2-chloro-4-({3-cyano-6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinoliny l}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)anili no]-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)a nilino]-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)a nilino]-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)et hoxy]-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)et hoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; cccccc) 7-ethoxy-6-nitro-4-[4-[(4-phenyl-1,3-thiazol-2-yl)sulfanyl]-3-(trifluorome thyl)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-(trifluorome thyl)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-(trif luoromethyl)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-quinolin ecarbonitrile or a pharmaceutically acceptable salt thereof; gggggg) 6-amino-4-[3-chloro-4-(1H-imidazol-1-ylmethyl)anilino]-7-ethoxy-3-quinolin ecarbonitrile or a pharmaceutically acceptable salt thereof; hhhhhh) (E)-N-{4-[3-chloro-4-(1H-imidazol-1-ylmethyl)anilino]-3-cyano-7-ethoxy-6-q uinolinyl}-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-ni tro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; mmmmmm) 6-amino-4-{3-chloro-4-[(4,6-dimethyl-2-pyrimidinyl)sulfanyl]anilino}-7-eth oxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; nnnnnn) (E)-N-(4-{3-chloro-4-[(4,6-dimethyl-2-pyrimidinyl)sulfanyl]anilino}-3-cyan o-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)propox y]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; pppppp) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(1H-tetraazol-1-ylmethyl)anili no]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; qqqqqq) 6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-[4-(2H-tetraazol-2-ylmethyl)anili no]-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-m ethoxy-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-q uinolinecarbonitrile or a pharmaceutically acceptable salt thereof; wwwwww) 6-methoxy-4-{4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]anilino}-7-[3-(4-morph olinyl)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}amin o)-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 ##STR52## 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: ##STR53## 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(CH.sub.2).sub.m --, --O(CH.sub.2).sub.m --, --S(CH.sub.2).sub.m --, --NR(CH.sub.2).sub.m --, --(CH.sub.2).sub.m -- --(CH.sub.2).sub.m NH--, --(CH.sub.2).sub.m O--, --(CH.sub.2).sub.m S--, or --(CH.sub.2).sub.m NR--; 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 --CH.sub.2 NH-- or --CH.sub.2 O--; 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; G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl 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, ##STR54## R.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y--; or R1 and R4 are as defined above and G.sub.1 or G.sub.2 or both are R.sub.2 --NH--; or if any of the substituents R.sub.1, G.sub.2, G.sub.3, or R.sub.4 are located on contiguous carbon atoms then they may be taken together as the divalent radical --O--C(R.sub.6).sub.2 --O--; Y is a divalent radical selected from the group consisting of ##STR55## R.sub.7 is --NR.sub.6 R.sub.6, --OR.sub.6, --J, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6); M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.p NR.sub.6 R.sub.6, or >N--(C(R.sub.6).sub.2).sub.p --OR.sub.6 ; W is >NR.sub.6, --O-- or is a bond; Het is 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 ##STR56## wherein Het is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.s OR.sub.6 or --(C(R.sub.6).sub.2).sub.s N(R.sub.6).sub.2, and optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.s O--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; R.sub.2, is selected from the group consisting of ##STR57## R.sub.3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR58## R.sub.7 --(C(R.sub.6).sub.2).sub.s --, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.r --, R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.r --, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r --; R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR59## R.sub.7 --(C(R.sub.6).sub.2).sub.s --, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.r --, R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.r --, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r --; R.sub.8, and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.r NR.sub.6 R.sub.6, or --(C(R.sub.6).sub.2).sub.r OR.sub.6 ; J is independently hydrogen, chlorine, fluorine, or bromine; Q is alkyl of 1-6 carbon atoms or hydrogen; a=0 or 1; g=1-6; k=0-4; n is 0-1; 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 R.sub.6 is alkenyl of 2-7 carbon atoms or alkynyl of 2-7 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6 -- and R.sub.7 is --NR.sub.6 R.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6), then g=2-6; when M is --O-- and R.sub.7 is --OR.sub.6 then p=1-4; when Y is --NR.sub.6 -- then k=2-4; when Y is --O-- and M or W is --O-- then k=1-4 when W is not a bond with Het bonded through a nitrogen atom then q=2-4 and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6 -- then k=2-4. 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 ##STR60## 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: ##STR61## 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(CH.sub.2).sub.m --, --O(CH.sub.2).sub.m --, --S(CH.sub.2).sub.m --, --NR(CH.sub.2).sub.m --, --(CH.sub.2).sub.m -- --(CH.sub.2).sub.m NH--, --(CH.sub.2).sub.m O--, --(CH.sub.2).sub.m S--, or --(CH.sub.2).sub.m NR--; 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 --CH.sub.2 NH-- or --CH.sub.2 O--; 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; G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR62## R.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y--; or R1 and R4 are as defined above and G.sub.1 or G.sub.2 or both are R.sub.2 --NH--; or if any of the substituents R.sub.1, G.sub.2, G.sub.3, or R.sub.4 are located on contiguous carbon atoms then they may be taken together as the divalent radical --O--C(R.sub.6).sub.2 --O--; Y is a divalent radical selected from the group consisting of ##STR63## R.sub.7 is --NR.sub.6 R.sub.6, --OR.sub.6, --J, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6); M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.p NR.sub.6 R.sub.6, or >N--(C(R.sub.6).sub.2).sub.p --OR.sub.6 ; W is >NR.sub.6, --O-- or is a bond; Het is 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 ##STR64## wherein Het is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.s OR.sub.6 or --(C(R.sub.6).sub.2).sub.s N(R.sub.6).sub.2, and optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.s O--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; R.sub.2, is selected from the group consisting of ##STR65## R.sub.3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR66## R.sub.7 --(C(R.sub.6).sub.2).sub.s --, R.sub.7 (C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.r --, R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.r --, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r--; R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR67## R.sub.7 --(C(R.sub.6).sub.2).sub.s --, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.r --, R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.r --, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r--; R.sub.8, and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.r NR.sub.6 R.sub.6, or --(C(R.sub.6).sub.2).sub.r OR.sub.6 ; J is independently hydrogen, chlorine, fluorine, or bromine; Q is alkyl of 1-6 carbon atoms or hydrogen; a=0 or 1; g=1-6; k=0-4; n is 0-1; 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 R.sub.6 is alkenyl of 2-7 carbon atoms or alkynyl of 2-7 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6 -- and R.sub.7 is --NR.sub.6 R.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6), then g=2-6; when M is --O--and R.sub.7 is --OR.sub.6 then p=1-4; when Y is --NR.sub.6 -- then k=2-4; when Y is --O--and M or W is --O-- then k=1-4 when W is not a bond with Het bonded through a nitrogen atom then q=2-4 and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6 -- then k=2-4. 15. A pharmaceutical composition which comprises a compound of formula 1 having the structure ##STR68## 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: ##STR69## 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(CH.sub.2).sub.m --, --O(CH.sub.2).sub.m --, --S(CH.sub.2).sub.m --, --NR(CH.sub.2).sub.m --, --(CH.sub.2).sub.m -- --(CH.sub.2).sub.m NH--, --(CH.sub.2).sub.m O--, --(CH.sub.2).sub.m S--, or --(CH.sub.2).sub.m NR--; 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 --CH.sub.2 NH-- or --CH.sub.2 O--; 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; G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR70## R.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y--; or R1 and R4 are as defined above and G.sub.1 or G.sub.2 or both are R.sub.2 --NH--; or if any of the substituents R.sub.1, G.sub.2, G.sub.3, or R.sub.4 are located on contiguous carbon atoms then they may be taken together as the divalent radical --O--C(R.sub.6).sub.2 --O--; Y is a divalent radical selected from the group consisting of ##STR71## R.sub.7 is --NR.sub.6 R.sub.6, --OR.sub.6, --J, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6); M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.p NR.sub.6 R.sub.6, or >N--(C(R.sub.6).sub.2).sub.p --OR.sub.6 ; W is >NR.sub.6, --O-- or is a bond; Het is 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 ##STR72## wherein Het is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.s OR.sub.6 or --(C(R.sub.6).sub.2).sub.s N(R.sub.6).sub.2, and optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.s O--; R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms; with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; R.sub.2, is selected from the group consisting of ##STR73## ##STR74## R.sub.3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR75## R.sub.7 --(C(R.sub.6).sub.2).sub.s --, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.r --, R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.r --, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r --; R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR76## R.sub.7 --(C(R.sub.6).sub.2).sub.s --, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.r --, R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.r --, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r --; R.sub.8, and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.r NR.sub.6 R.sub.6, or --(C(R.sub.6).sub.2).sub.r OR.sub.6 ; J is independently hydrogen, chlorine, fluorine, or bromine; Q is alkyl of 1-6 carbon atoms or hydrogen; a=0 or 1; g=1-6; k=0-4; n is 0-1; 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 R.sub.6 is alkenyl of 2-7 carbon atoms or alkynyl of 2-7 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; and further provided that when Y is --NR.sub.6 -- and R.sub.7 is --NR.sub.6 R.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6), then g=2-6; when M is --O-- and R.sub.7 is --OR.sub.6 then p=1-4; when Y is --NR.sub.6 -- then k=2-4; when Y is --O-- and M or W is --O-- then k=1-4 when W is not a bond with Het bonded through a nitrogen atom then q=2-4 and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6 -- then k=2-4 and a pharmaceutical carrier.