Details for Patent: 6,297,258

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), Frost; Philip (Morris Township, NJ)
Assignee:	American Cyanamid Company (Madison, NJ)
Filing Date:	Aug 01, 2000
Application Number:	09/630,270
Claims:	1. A compound of Formula 1 having the structure: ##STR44## wherein: X is cycloalkyl of 3 to 7 carbon atoms, which may be optionally substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a pyridinyl, pyrimidinyl, or phenyl ring wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalky of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, methylmercapto, and benzoylamino; Z is --NH--, --O--, --S--, or --NR--; R is alkyl of 1-6 carbon atoms, or carboalkyl of 2-7 carbon atoms; G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR45## R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.k --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y-- with the proviso that either G.sub.1 or G.sub.2 or both G.sub.1 and G.sub.2 must be a radical selected from the group ##STR46## R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.k --Y--, R'.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y--, or ##STR47## Y is a divalent radical selected from the group consisting of ##STR48## R.sub.7 is --NR.sub.6 R.sub.6, --J, --OR.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6); R'.sub.7 is --N(OR.sub.6), --N(R.sub.6).sub.3.sup.+, alkenoxy of 1-6 carbon atoms, alkynoxy of 1-6 carbon atoms, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, N-alkyl-N-alkynylamino of 4 to 12 carbon atoms, N-alkenyl-N-alkynylamino of 4 to 12 carbon atoms, or N,N-dialkynylamino of 6-12 carbon atoms with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.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 a heterocycle selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, pyridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, thiazole, thiazolidine, tetrazole, piperazine, furan, thiophene, tetrahydrothiophene, tetrahydrofuran, dioxane, 1,3-dioxolane, tetrahydropyran, and ##STR49## wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.S OR.sub.6 or --(C(R.sub.6).sub.2).sub.S N(R.sub.6).sub.2, or optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.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; R.sub.2, is selected from the group consisting of ##STR50## ##STR51## 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, ##STR52## 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 --; with the proviso that at least one of the R.sub.3 groups is selected from the group ##STR53## 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 --; with the proviso that for said at least one R.sub.3 group the moiety Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2)r-- cannot be morpholino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, piperidino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, N-alkyl piperidino-N-alkyl wherein either alkyl group is 1-6 carbon atoms, or azacycloalkyl-N-alkyl of 3-11 carbon atoms; R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR54## 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; 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 optionally substituted phenyl or a pharmaceutically acceptable salt thereof. 4. The compound according to claim 3 wherein R.sub.1 and R.sub.4 are hydrogen or a pharmaceutically acceptable salt thereof. 5. The compound according to claim 1, which is: a) 1-Methyl-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid[4-(3-bromo-phenylamino)-3-cyano-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; b) N-[4-[(3-Bromophenyl)amino]-3-cyano-6-quinolinyl]-4-(N-allyl-N-methylamino )-2-butynamide or a pharmaceutically acceptable salt thereof; c) N-[4-[(3-Bromophenyl)amino]-3-cyano-6-quinolinyl]-4-(N-methoxyethyl-N-meth ylamino)-2-butynamide or a pharmaceutically acceptable salt thereof; d) N-[4-[(3-Bromophenyl)amino]-3-cyano-6-quinolinyl]-4-(bis-(2-methoxyethyl)a mino)-2-butynamide or a pharmaceutically acceptable salt thereof; e) 4-Methoxymethoxy-but-2-ynoic acid[4-(3-bromo-phenylamino)-3-cyano-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; f) 4-(4-Chloro-2-fluoro-phenylamino)-6-methoxy-7-(2-pyridin-4-yl-ethoxy)-1-qu inoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; g) 4-(2-Methoxy-ethoxy)-but-2-ynoic acid[4-(3-bromo-phenylamino)-3-cyano-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; h) 4-((2S)-2-Methoxymethylpyrrolidin-1-yl)but-2-ynoic Acid[4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]amide or a pharmaceutically acceptable salt thereof; i) 4-(1,4-Dioxa-8-azaspiro[4,5]dec-8-yl)but-2-ynoic Acid[4-(3-Bromophenylamino)-3-cyanoquinolin-6-yl]amide or a pharmaceutically acceptable salt thereof; j) 4-(3-Bromo-phenylamino)-6-(2-ethoxy-3,4-dioxo-cyclobut-1-enylamino)-quinol ine-3-carbonitrile or a pharmaceutically acceptable salt thereof; k) 4-[(2-Methoxy-ethyl)-methyl-amino]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; l) (S)-4-(2-Methoxymethyl-pyrrolidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide dihydrochloride or a pharmaceutically acceptable salt thereof; m) 4-(3-Hydroxymethyl-piperidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; n) 4-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; o) 4-(2-Hydroxymethyl-piperidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; p) 4-Bromo-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; q) 4-(3-hydroxy-4-methyl-phenylamino)-6-methoxy-7-(3-pyridin-4-yl-propoxy)-qu inoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; r) 4-Diallylamino-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3cyano-7-methoxy-quinolin-6-yl]-ami de or a pharmaceutically acceptable salt thereof; s) 4-[Bis-(2-methoxy-ethyl)-amino]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; t) 4-([1,3]Dioxolan-2-ylmethyl-methyl-amino)-but-2-enoic acid3-cyano-7-methoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; u) 4-[Bis-(2-hydroxy-ethyl)-amino]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy- quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; v) 4-Thiomorpholin-4-yl-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; w) 4-[4-(2-Hydroxy-ethyl)-piperazin-1-yl]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy- quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; x) 4-(1,4,7-Trioxa-10-aza-cyclododec-10-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy- quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; y) 4-(Methoxy-methyl-amino)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; z) 4-(4-Hydroxy-piperidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; aa) 4-[1,4']Bipiperidinyl-1'-yl-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; bb) 4-Thiazolidin-3-yl-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; cc) 3-{3-[4-(3-Chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-ylcar bamoyl]-allyl}-4-methyl-thiazol-3-ium bromide or a pharmaceutically acceptable salt thereof; dd) 4-(2,6-Dimethyl-piperidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; ee) 4-[Bis-(2-hydroxy-propyl)-amino]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; ff) 4-(3-Hydroxy-pyrrolidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; gg) 4-[(2-Hydroxy-ethyl)-methyl-amino]-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; hh) 4-(2,5-Dimethyl-pyrrolidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; ii) 4-(4,4-Dihydroxy-piperidin-1-yl)-but-2-enoic acid[4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-am ide or a pharmaceutically acceptable salt thereof; jj) 4-(3-Chloro-4-fluoro-phenylamino)-7-methoxy-6-pyrrolidin-1-yl-quinoline-3- carbonitrile or a pharmaceutically acceptable salt thereof; kk) 4-(3-Chloro-4-fluroanilino)-7-methoxy-6-(1H-pyrrol-1-yl)-3-quinolinecarbon itrile or a pharmaceutically acceptable salt thereof; ll) 6-(1-Aziridinyl)-4-(3-chloro-4-fluoroanilino)-7-methoxy-3-quinolinecarboni trile or a pharmaceutically acceptable salt thereof; mm) 4-[(2-Methoxy-ethyl)-methyl-amino]-but-2-enoic acid[4-(3-bromo-phenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof; nn) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-[3-(4-hydroxy-piperidin-1-yl)-pro poxy]-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; oo) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-{3-[4-(2-hydroxy-ethyl)-piperazin -1-yl]-propoxy}-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; pp) 4-(2-Bromo-4-chloro-phenylamino)-7-{2-[(2-hydroxy-ethyl)-methyl-amino]-eth oxy}-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; qq) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-{3-[(2-hydroxy-ethyl)-methyl-amin o]-propoxy}-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; rr) 4-(2,4-Dichloro-5-methoxy-phenylamino)-6-methoxy-7-(3-thiomorpholin-4-yl-p ropoxy)-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ss) 4-(2,4-Dichloro-5-methoxy-phenylamino)-6-methoxy-7-[3-(2-methoxy-ethylamin o)-propoxy]-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; tt) 4-(2,4-Dichloro-5-methoxy-phenylamino)-6-methoxy-7-[3-(4-methyl-piperidin- 1-yl)-propoxy]-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; uu) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-[3-(2,6-dimethyl-morpholin-4-yl)- propoxy]-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; vv) 4-(2-Bromo-4-chloro-phenylamino)-7-{2-[4-(2-hydroxy-ethyl)-piperazin-1-yl] -ethoxy}-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ww) 4-(2-Bromo-4-chloro-phenylamino)-7-[2-(4-hydroxy-piperidin-1-yl)-ethoxy]-6 -methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; xx) 4-(2-Bromo-4-chloro-phenylamino)-6-methoxy-7-(2-thiomorpholin-4-yl-ethoxy) -quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; yy) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-[3-(2,5-dimethyl-pyrrolidin-1-yl) -propoxy]-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; zz) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-[3-(3-hydroxy-propylamino)-propox y]-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; aaa) 1-{3-[3-Cyano-4-(2,4-dichloro-5-methoxy-phenylamino)-6-methoxy-quinolin-7- yloxy]-propyl}-piperidine-4-carboxylic acid ethyl ester or a pharmaceutically acceptable salt thereof; bbb) 7-[3-(4-acetyl-1-piperazinyl)propoxy]-4-[(2,4-dichloro-5-methoxyphenyl)ami no]-6-methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ccc) 4-(3-chloro-4-fluoroanilino)-7-methyoxy-6(4-morpholinyl)-3-quinolinecarbon itrile or a pharmaceutically acceptable salt thereof; ddd) 7-[3-(4-Benzyl-piperazin-1-yl)-propoxy]-4-(2,4-dichloro-5-methoxy-phenylam ino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; eee) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-[3-(2-hydroxy-ethylamino)-propoxy ]-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; fff) 4-(2,4-Dichloro-5-methoxy-phenylamino)-7-{3-[ethyl-(2-hydroxy-ethyl)-amino ]-propoxy}-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; ggg) 7-{3-[Bis-(2-methoxy-ethyl)-amino]-propoxy}-4-(2,4-dichloro-5-methoxy-phen ylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; hhh) 7-{3-[Bis-(2-hydroxy-ethyl)-amino]-propoxy}-4-(2,4-dichloro-5-methoxy-phen ylamino)-6-methoxy-quinoline-3-carbonitrile or a pharmaceutically acceptable salt thereof; iii) 4-(3-chloro-4-fluoroanilino)-7-(4-morpholinyl)-6-nitro-3-quinolinecarbonit rile or a pharmaceutically acceptable salt thereof; jjj) N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-(4-morpholinyl)-6-quinolinyl]-2- butynamide or a pharmaceutically acceptable salt thereof; kkk) 6-amino-4-(3-chloro-4-fluoroanilino)-7-(4-morpholinyl)-3-quinolinecarbonit rile or a pharmaceutically acceptable salt thereof; lll) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-(3-{[2-(4-morpholinyl)ethyl] amino}propoxy)-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; mmm) 7-{3-[(2-anilinoethyl)amino]propoxy}-4-(2,4-dichloro-5-methoxyanilino)-6-m ethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; nnn) N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-(4-morpholinyl)-6-quinolinyl]acr ylamide or a pharmaceutically acceptable salt thereof; ooo) 4-(3-chloro-4-fluoroanilino)-7-{4-[2-(dimethylamino)ethyl]-1-piperazinyl}- 6-nitro-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ppp) 6-amino-4-(3-chloro-4-fluoroanilino)-7-{4-[2-(dimethylamino)ethyl]-1-piper azinyl}-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; qqq) N-(4-(3-chloro-4-fluoroanilino)-3-cyano-7-{4-[2-(dimethylamino)ethyl]-1-pi perazinyl}-6-quinolinyl)acrylamide or a pharmaceutically acceptable salt thereof; rrr) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-({2-[4-(2-methoxyethyl)-1-pi perazinyl]ethyl}amino)-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; sss) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(2H-1,2,3-triazol-2-yl)pr opoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ttt) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(1H-1,2,3-triazol-1-yl)pr opoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; uuu) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-(3-thienyl)-3-quinolinecarbo nitrile or a pharmaceutically acceptable salt thereof; vvv) 4-[(E)-2-(2-quinolinyl)ethenyl]aniline or a pharmaceutically acceptable salt thereof; www) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-{[2-(2H-1,2,3-triazol-2-yl)e thyl]amino}-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; xxx) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-{[2-(1H-1,2,3-triazol-1-yl)e thyl]amino}-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; yyy) 4-(2,4-dichloro-5-methoxyanilino)-7-(3-thienyl)-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; zzz) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(1H-1,2,4-triazol-1-yl)pr opoxy]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; aaaa) 4-(2,4-dichloro-5-methoxyanilino)-7-[3-(1H-imidazol-1-yl)propoxy]-6-methox y-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; bbbb) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(1H-pyrazol-1-yl)propoxy] -3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; cccc) N-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-quinolinyl]-N-[4- (4-ethyl-1-piperazinyl)butyl]acetamide or a pharmaceutically acceptable salt thereof; dddd) N-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-quinolinyl]-N-(3- (4-ethyl-1-piperazinyl)propyl)acetamide or a pharmaceutically acceptable salt thereof; eeee) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-{3-[4-(2-methoxyethyl)-1-pip erazinyl]propoxy}-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; ffff) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-(1H-pyrrol-1-yl)-3-quinoline carbonitrile or a pharmaceutically acceptable salt thereof; gggg) 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]- 3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; hhhh) 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-[2-(2H-1,2,3-triazol-2-yl)ethoxy]- 3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; iiii) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(1H-tetraazol-1-yl)propox y]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; jjjj) 4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(2H-tetraazol-2-yl)propox y]-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; kkkk) 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]- 3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; llll) 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-[2-(2H-1,2,3-triazol-2-yl)ethoxy]- 3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof; or mmmm) 4-(2,4-dichloro-5-methoxyanilino)-7-{3-[[2-(dimethylamino)ethyl](methyl)am ino]propoxy}-6-methoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof. 6. A method of treating, inhibiting the growth of, or eradicating a neoplasm in a mammal in need thereof which comprises administering to said mammal an effective amount of a compound of Formula 1 having the structure ##STR55## wherein: X is cycloalkyl of 3 to 7 carbon atoms, which may be optionally substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a pyridinyl, pyrimidinyl, or phenyl ring wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalky of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, methylmercapto, and benzoylamino; Z is --NH--, --O--, --S--, or --NR--; R is alkyl of 1-6 carbon atoms, or carboalkyl of 2-7 carbon atoms; G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR56## R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.k --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y-- with the proviso that either G.sub.1 or G.sub.2 or both G.sub.1 and G.sub.2 must be a radical selected from the group ##STR57## R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.k --Y--, R'.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y--, or ##STR58## Y is a divalent radical selected from the group consisting of ##STR59## R.sub.7 is --NR.sub.6 R.sub.6, -J, --OR.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6); R'.sub.7 is --NR.sub.6 (OR.sub.6), --N(R.sub.6).sub.3.sup.+, alkenoxy of 1-6 carbon atoms, alkynoxy of 1-6 carbon atoms, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, N-alkyl-N-alkynylamino of 4 to 12 carbon atoms, N-alkenyl-N-alkynylamino of 4 to 12 carbon atoms, or N,N-dialkynylamino of 6-12 carbon atoms with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.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 a heterocycle selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, pyridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, thiazole, thiazolidine, tetrazole, piperazine, furan, thiophene, tetrahydrothiophene, tetrahydrofuran, dioxane, 1,3-dioxolane, tetrahydropyran, and ##STR60## wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.s OR.sub.6 or --(C(R.sub.6).sub.2).sub.s N(R.sub.6).sub.2, or optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.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; R.sub.2, is selected from the group consisting of ##STR61## ##STR62## 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, ##STR63## 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 --; with the proviso that at least one of the R.sub.3 groups is selected from the group ##STR64## 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 --; with the proviso that for said at least one R.sub.3 group the moiety Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r -- cannot be morpholino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, piperidino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, N-alkyl piperidino-N-alkyl wherein either alkyl group is 1-6 carbon atoms, or azacycloalkyl-N-alkyl of 3-11 carbon atoms; R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR65## 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; 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. 7. The method according to claim 6 wherein the neoplasm is selected from the group consisting of breast, kidney, bladder, mouth, larynx, esophagus, stomach, colon, ovary, and lung. 8. A method of treating, inhibiting the progression of, or eradicating polycystic kidney disease in a mammal in need thereof which comprises administering to said mammal an effective amount of a compound of formula 1 having the structure ##STR66## wherein: X is cycloalkyl of 3 to 7 carbon atoms, which may be optionally substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a pyridinyl, pyrimidinyl, or phenyl ring wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalky of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, methylmercapto, and benzoylamino; Z is --NH--, --O--, --S--, or --NR--; R is alkyl of 1-6 carbon atoms, or carboalkyl of 2-7 carbon atoms; G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR67## R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.k --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y-- with the proviso that either G.sub.1 or G.sub.2 or both G.sub.1 and G.sub.2 must be a radical selected from the group ##STR68## R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.k --Y--, R'.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y--, or R.sub.2 --N.sup.H--; Y is a divalent radical selected from the group consisting of ##STR69## R.sub.7 is --NR.sub.6 R.sub.6, --J, --OR.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6), R'.sub.7 is --NR.sub.6 (OR.sub.6), --N(R.sub.6).sub.3.sup.+, alkenoxy of 1-6 carbon atoms, alkynoxy of 1-6 carbon atoms, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, N-alkyl-N-alkynylamino of 4 to 12 carbon atoms, N-alkenyl-N-alkynylamino of 4 to 12 carbon atoms, or N,N-dialkynylamino of 6-12 carbon atoms with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.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 a heterocycle selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, pyridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, thiazole, thiazolidine, tetrazole, piperazine, furan, thiophene, tetrahydrothiophene, tetrahydrofuran, dioxane, 1,3-dioxolane, tetrahydropyran, and ##STR70## wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.s OR.sub.6 or --(C(R.sub.6).sub.2).sub.s N(R.sub.6).sub.2, or optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.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; R.sub.2, is selected from the group consisting of ##STR71## ##STR72## 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, ##STR73## 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 --; with the proviso that at least one of the R.sub.3 groups is selected from the group ##STR74## 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 --; with the proviso that for said at least one R.sub.3 group the moiety Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r -- cannot be morpholino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, piperidino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, N-alkyl piperidino-N-alkyl wherein either alkyl group is 1-6 carbon atoms, or azacycloalkyl-N-alkyl of 3-11 carbon atoms; R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##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.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; 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. 9. A pharmaceutical composition which comprises a compound of formula 1 having the structure ##STR76## wherein: X is cycloalkyl of 3 to 7 carbon atoms, which may be optionally substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a pyridinyl, pyrimidinyl, or phenyl ring wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalky of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, methylmercapto, and benzoylamino; Z is --NH--, --O--, --S--, or --NR--; R is alkyl of 1-6 carbon atoms, or carboalkyl of 2-7 carbon atoms; G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR77## R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.k --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y-- with the proviso that either G.sub.1 or G.sub.2 or both G.sub.1 and G.sub.2 must be a radical selected from the group ##STR78## R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.k --Y--, R'.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y--, or ##STR79## Y is a divalent radical selected from the group consisting of ##STR80## R.sub.7 is --NR.sub.6 R.sub.6, -J, --OR.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6); R'.sub.7 is --NR.sub.6 (OR.sub.6), --N(R.sub.6).sub.3.sup.+, alkenoxy of 1-6 carbon atoms, alkynoxy of 1-6 carbon atoms, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, N-alkyl-N-alkynylamino of 4 to 12 carbon atoms, N-alkenyl-N-alkynylamino of 4 to 12 carbon atoms, or N,N-dialkynylamino of 6-12 carbon atoms with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom; M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.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 a heterocycle selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, pyridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, thiazole, thiazolidine, tetrazole, piperazine, furan, thiophene, tetrahydrothiophene, tetrahydrofuran, dioxane, 1,3-dioxolane, tetrahydropyran, and ##STR81## wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.s OR.sub.6 or --(C(R.sub.6).sub.2).sub.s N(R.sub.6).sub.2, or optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.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; R.sub.2, is selected from the group consisting of ##STR82## ##STR83## 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, ##STR84## 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 --; with the proviso that at least one of the R.sub.3 groups is selected from the group ##STR85## 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 --; with the proviso that for said at least one R.sub.3 group the moiety Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r -- cannot be morpholino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, piperidino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, N-alkyl piperidino-N-alkyl wherein either alkyl group is 1-6 carbon atoms, or azacycloalkyl-N-alkyl of 3-11 carbon atoms; R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR86## 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; 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.