Substituted 3-cyano quinolines

• US 6,002,008 A
• Filed: 03/27/1998
• Issued: 12/14/1999
• Est. Priority Date: 04/03/1997
• Status: Expired due to Term

• Current Assignee: Wyeth Holdings LLC (Pfizer Inc.)
• Original Assignee: American Cyanamid Co (Pfizer Inc.)
• Inventors: Reich, Marvin F., Kitchen, Douglas B., Tsou, Hwei-Ru, Floyd, Middleton B. Jr., Wissner, Allan, Johnson, Bernard D.
• Primary Examiner(s): SEAMAN, D MARGARET M
• Application Number:
  US09/049,718
• Time in Patent Office: 627 Days
• Field of Search: 546/153, 546/156, 546/157, 546/159, 546/150, 546/161, 514/312, 514/313
• US Class Current: 546/160
• CPC Class Codes: C07D 215/54 attached in position 3
• CPC Class Codes: C07D 215/56 with oxygen atoms in position 4
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links

Abstract

This invention provides compounds having the formula: ##STR1## wherein: X is cycloalkyl which may be optionally substituted; or is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally substituted;

n is 0-1;

Y is --NH--, --O--, --S--, or --NR--;

R is alkyl of 1-6 carbon atoms;

R₁, R₂, R₃, and R₄ are each, independently, hydrogen, halogen, alkyl, alkenyl, alkynyl, alkenyloxy, alkynyloxy, hydroxymethyl, halomethyl, alkanoyloxy, alkenoyloxy, alkynoyloxy, alkanoyloxymethyl, alkenoyloxymethyl, alkynoyloxymethyl, alkoxymethyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulfonamido, alkenylsulfonamido, alkynylsulfonamido, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy, carboalkyl, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino, alkylamino, dialkylamino, aminoalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, phenylamino, benzylamino, ##STR2## R₅ is alkyl which may be optionally substituted, or phenyl which may be optionally substituted;

R₆ is hydrogen, alkyl, or alkenyl;

R₇ is chloro or bromo

R₈ is hydrogen, alkyl, aminoalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, N-cycloalkylaminoalkyl, N-cycloalkyl-N-alkylaminoalkyl, N,N-dicycloalkylaminoalkyl, morpholino-N-alkyl, piperidino-N-alkyl, N-alkyl-piperidino-N-alkyl, azacycloalkyl-N-alkyl, hydroxyalkyl, alkoxyalkyl, carboxy, carboalkoxy, phenyl, carboalkyl+, chloro, fluoro, or bromo;

Z is amino, hydroxy, alkoxy, alkylamino, dialkylamino, morpholino, piperazino, N-alkylpiperazino, or pyrrolidino;

m=1-4,q=1-3, and p=0-3;

any of the substituents R₁, R₂, R₃, or R₄ that are located on contiguous carbon atoms can together be the divalent radical --O--C(R₈)₂ --O--;

or a pharmaceutically acceptable salt thereof with the proviso that when Y is --NH--, R₁, R₂, R₃, and R₄ are hydrogen, and n is 0, X is not 2-methylphenyl, which are inhibitors of protein tyrosine kinase.

Claims

1. A compound of the formula ##STR20## 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 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, and benzoylamino;

n is 0-1;

Y is --NH--, --O--, --S--, or --NR--;

R is alkyl of 1-6 carbon atoms;

R₁, R₂, R₃, and R₄ are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, 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, aminoalkyl of 1-4 carbon atoms, N-alkylaminoalkyl of 2-7 carbon atoms, N,N-dialkylaminoalkyl of 3-14 carbon atoms, phenylamino, benzylamino, ##STR21## R₅ is alkyl of 1-6 carbon atoms, alkyl optionally substituted with one or more halogen atoms, phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, nitro, cyano, or alkyl of 1-6 carbon atoms groups;

R₆ is hydrogen, alkyl of 1-6 carbon atoms, or alkenyl of 2-6 carbon atoms;

R₇ is chloro or bromo

R₈ is hydrogen, alkyl of 1-6 carbon atoms, aminoalkyl of 1-6 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-12 carbon atoms, N-cycloalkylaminoalkyl of 4-12 carbon atoms, N-cycloalkyl-N-alkylaminoalkyl of 5-18 carbon atoms, N,N-dicycloalkylaminoalkyl of 7-18 carbon atoms, 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, azacycloalkyl-N-alkyl of 3-11 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-8 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, chloro, fluoro, or bromo;

Z is amino, hydroxy, alkoxy of 1-6 carbon atoms, alkylamino wherein the alkyl moiety is of 1-6 carbon atoms, dialkylamino wherein each of the alkyl moieties is of 1-6 carbon atoms, morpholino, piperazino, N-alkylpiperazino wherein the alkyl moiety is of 1-6 carbon atoms, or pyrrolidino;

m=1-4, q=1-3, and p=0-3;

any two of the substituents R₁, R₂, R₃, or R₄ that are located on contiguous carbon atoms can together be the divalent radical --O--C(R₈)₂ --O--;

or a pharmaceutically acceptable salt thereof with the proviso that when Y is --NH--, R₁, R₂, R₃, and R₄ are hydrogen, and n is 0, X is not 2-methylphenyl further provided that R³ ≠

Cl.

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

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

4. The compound according to claim 3 wherein R₁ and R₄ are hydrogen or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 which is 4-[(3-bromophenyl)amino]-6,7-diethoxy-3-quinolinecarbonitrile or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 which is 4dimethylamino-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1 which is 4-diethylamino-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 which is 4-dimethylamino-but-2-enoic acid [4-(3-bromo-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 1 which is 4dimethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 1 which is 4-diethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 1 which is 4-morpholin-4-yl-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 1 which is 4-dimethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 which is N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-methoxy-2-butynamide or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 1 which is N-{4-[(3-chloro-4-fluorophenyl)-amino]-3-cyano-6-quinolinyl}-4-dimethylamino-2-butenamide or a pharmaceutically acceptable salt thereof.

15. A compound according to claim 1 which is

a) 4-[(3-bromophenyl)amino]-7-methoxy-3-quinolinecarbonitrile;

b) 4-[(3-bromophenyl)amino]-7-methoxy-6-nitro-3-quinolinecarbonitrile;

c) 6-amino-4-[(3-bromophenyl)amino]-7-methoxy-3-quinolinecarbonitrile;

d) N-[4-[(3-bromophenyl)amino]-3-cyano-7-methoxy-6-quinolinyl]-2-butynamide;

e) N-[4-[(3-bromophenyl)amino]-3-cyano-7-methoxy-6-quinolinyl]-2-propenamide;

f) 4-[(3-bromophenyl)amino]-6-nitro-3-quinolinecarbonitrile;

g) 6-amino-4-[(3-bromophenyl)amino] -3-quinolinecarbonitrile;

h) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-2-butynamide;

i) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]acetamide;

j) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]butanamide;

k) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-2-propenamide;

l) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-2-chloroacetamide;

m) 4-[(3,4-dibromophenyl)amino]-6-nitro-3-quinolinecarbonitrile;

n) 6-amino-4-[(3,4-dibromophenyl)amino]-3-quinolinecarbonitrile;

o) N-[4-[(3,4-dibromophenyl)amino]-3-cyano-6-quinolinyl]-2-butynamide;

p) 6-nitro-4-[(3-trifluoromethylphenyl)amino]-3-quinolinecarbonitrile;

q) 6-amino-4-[(3-trifluoromethylphenyl)amino]-3-quinolinecarbonitrile;

r) N-[4-[(3-trifluoromethylphenyl)amino]-3-cyano-6-quinolinyl]-2-butynamide;

s) 4-[(3-bromophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile;

t) 4-[(3-fluorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile;

u) 4-(cyclohexyamino)-6,7-dimethoxy-3-quinolinecarbonitrile;

v) 4-[(3-bromophenyl)amino]-6,7-dihydroxy-3-quinolinecarbonitrile;

w) 8-[(3-bromophenyl)amino]-[1,3]-dioxolo[4,5-g]quinoline-7-carbonitrile;

x) 4-[(3-chlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile;

y) 4-[(3-trifluoromethylphenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile;

z) 4-[(3,4-dimethoxyphenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile;

aa) 4-[(methylphenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile;

bb) 4-[(3-cyanophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile;

cc) 4-[(4-fluorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile;

dd) 4-[(3-(hydroxymethyl)phenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile;

ee) 4-(3-bromophenoxy)-6,7-dimethoxy-3-quinolinecarbonitrile;

ff) 4-[(4-bromophenyl)sulfanyl]-6,7-dimethoxy-3-quinolinecarbonitrile;

gg) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-3(E)-chloro-2-propenamide;

hh) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-3(Z)-chloro-2-propenamide;

ii) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-2-methyl-2-propenamide;

jj) N-[4-[(3,4-dibromophenyl)amino]-3-cyano-6-quinolinyl]-2-propenamide;

kk) N-[4-[(5-bromo-3-pyridinyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile;

ll) 4-[(3-bromophenyl)amino]-6,7-bis(methoxymethoxy)-3-quinolinecarbonitrile;

mm) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-hydroxy-2-butynamide;

nn) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-morpholino-2-butynamide;

oo) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-dimethylamino-2-butynamide;

pp) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-methoxy-2-butynamide;

qq) 4-(3-bromophenylmethylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

rr) 4-(3-phenylmethylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

ss) 4-(3,4-dimethoxyphenylmethylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

tt) 4-(3,4-dichlorophenylmethylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

uu) 4-methoxy-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyanoquinolin-6-yl]-amide;

vv) 4-(4-chloro-2-fluoro-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile;

ww) 4-(4-chloro-2-fluoro-phenylamino)-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrile;

xx) 7-(2-dimethylamino-ethoxy)-4-(3-hydroxy-4-methyl-phenylamino)-6-methoxy-quinoline-3-carbonitrile;

yy) 4-(3-hydroxy-4-methyl-phenylamino)-6-methoxy-7-(2-morpholin-4-yl-ethoxy)-quinoline-3-carbonitrile;

or

zz) 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(3-dimethylamino-propoxy)-6-methoxy-quinoline-3-carbonitrile;

or a pharmaceutically acceptable salt thereof.

16. A compound according to claim 1 which is

a) 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrile;

b) 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(2-dimethylamino-ethoxy)-6-methoxy-quinoline-3-carbonitrile;

c) 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-6-methoxy-7-(2-morpholin-4-yl-ethoxy)-quinoline-3-carbonitrile;

d) N-[3-cyano-4-(3-fluorophenylamino)quinolin-6-yl]acrylamide;

e) 6,7-dimethoxy-4-(3-nitrophenylamino)quinoline-3-carbonitrile;

f) 4-(3-bromophenylamino)-6-ethoxy-7-methoxyquinoline-3-carbonitrile;

g) 6-ethoxy-4-(3-hydroxy-4-methylphenylamino)-7-methoxyquinoline-3-carbonitrile;

h) 4-dimethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-quinolin-6-yl]-amide;

i) 4-diethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-quinolin-6-yl]-amide;

j) 4-methylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-quinolin-6-yl]-amide;

k) 4-[(3-bromophenyl)amino]-8-methyl-6-nitro-3-quinolinecarbonitrile;

l) 4-[(3-bromophenyl)amino]-8-dimethylaminomethyl-6-nitro-3-quinolinecarbonitrile;

m) 6-amino-4-[(3-bromophenyl)amino]-8-dimethylaminomethyl-3-quinolinecarbonitrile;

n) N-{4-[(3-bromophenyl)amino]-3-cyano-8-dimethylaminomethyl-6-quinolinyl}-2-butynamide;

o) N-{4-[(3-bromophenyl)amino]-3-cyano-8-dimethylaminomethyl-6-quinolinyl}-2-propenamide;

p) N-[4-[(3-bromophenyl)amino]-3-cyano-8-dimethylaminomethyl-6-quinolinyl}acetamide;

q) 4-[(3-chloro-4-fluorophenyl)amino]-7-methoxy-6-(morpholinopropoxy)-3-quinolinecarbonitrile;

r) 4-[(3-bromophenyl)amino]-7-methoxy-6-(morpholinopropoxy)-3-quinolinecarbonitrile;

s) 4-[(4chloro-2-fluorophenyl)amino]-7-methoxy-6-(morpholinopropoxy)-3-quinolinecarbonitrile;

t) 4-[(3-hydroxy-4-methylphenyl)amino]-7-methoxy-6-(morpholinopropoxy)-3-quinolinecarbonitrile;

u) N-{3-cyano-4-[(3-iodophenyl)amino]-6-quinolinyl}-2-propenamide;

v) 6-amino-4-[(3-iodophenyl)amino]-3-quinolinecarbonitrile;

w) 4-[(3-iodophenyl)amino]-6-nitro-3-quinolinecarbonitrile;

x) N-{3-cyano-4-[(3-methylphenyl)amino]-6-quinolinyl}-2-butynamide;

y) 6-amino-4-[(3-methylphenyl)amino]-3-quinolinecarbonitrile;

z) 6-nitro-4-[(3-methylphenyl)amino]-3-quinolinecarbonitrile;

aa) N-{4-[(3-chlorophenyl)amino]-3-cyano-6-quinolinyl}-2-propenamide;

bb) 6-amino-4-[(3-chlorophenyl)amino]-3-quinolinecarbonitrile;

cc) 4-[(3-chlorophenyl)amino]-6-nitro-3-quinolinecarbonitrile;

dd) N-{3-cyano-4-[(3-methoxyphenyl)amino]-6-quinolinyl}-2-propenamide;

ee) N-{3-cyano-4-[(3-methoxyphenyl)amino]-6-quinolinyl}-2-butynamide;

ff) N-{3-cyano-4-[(3-methoxyphenyl)amino]-6-quinolinyl}-4-piperidino-2-butynamide;

gg) 6-amino-4-[(3-methoxyphenyl)amino]-3-quinolinecarbonitrile;

hh) 4-[(3-methoxyphenyl)amino]-6-nitro-3-quinolinecarbonitrile;

ii) N-{4-[(3-chloro-4-fluoro-phenyl)amino]-3-cyano-6-quinolinyl}-2-butynamide;

jj) N-{4-[(3-chloro-4fluorophenyl)amino]-3-cyano-6-quinolinyl}-2-propenamide;

kk) N-{4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl}-4-diethylamino-2-butenamide;

ll) N-{4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl}-4-morpholino-2-butenamide;

mm) N-{4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl}-2-morpholin-4-ylmethyl-2-propenamide;

nn) 6-amino-[(3-chloro-4-fluorophenyl)amino]-3-quinolinecarbonitrile;

oo) 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-3-quinolinecarbonitrile;

pp) N-{4-[(4-bromophenyl)amino]-3-cyano-6-quinolinyl}-2-propenamide;

qq) 6-amino-4-[(4-bromophenyl)amino]-3-quinolinecarbonitrile;

rr) [(4-bromophenyl)amino]-6-nitro-3-quinolinecarbonitrile;

ss) N-{3-cyano-4-[(3,4-difluorophenyl)amino]-6-quinolinyl]-2-propenamide;

tt) 6-amino-4-[(3,4difluorophenyl)amino]-3-quinolinecarbonitrile;

uu) 4-[(3,4-difluorophenyl)amino]-6-nitro-3-quinolinecarbonitrile;

ww) N-{4-[(3-chloro-4-thiophenoxyphenyl)amino]-3-cyano-6-quinolinyl}-2-butynamide;

xx) 6-amino-4-[(3-chloro-4-thiophenoxyphenyl)amino]-3-quinolinecarbonitrile;

yy) 4-[(3-chloro-4-thiophenoxyphenyl)amino]-6-nitro-3-quinolinecarbonitrile;

or

zz) N-(3-cyano-4-[(3-cyanophenyl)amino]-6-quinolinyl}-2-propenamide;

or a pharmaceutically acceptable salt thereof.

17. A compound according to claim 1 which is

a) N-{3-cyano-4-[(3-cyanophenyl)amino]-6-quinolinyl}-4-piperidino-2-butynamide;

b) 6-amino-4-[(3-cyanophenyl)amino]-3-quinolinecarbonitrile;

c) 4-[(3-cyanophenyl)amino]-6-nitro-3-quinolinecarbonitrile;

d) N-{3-cyano-4-[(3-ethynylphenyl)amino]-6-quinolinyl}-2-butynamide;

e) N-{3-cyano-4-[(3-ethynylphenyl)amino]-6-quinolinyl}-2-propenamide;

f) N-{3-cyano-4-[(3-ethynylphenyl)amino]-6-quinolinyl}-4-piperidino-2-butynamide;

g) 6-amino-4-[(3-ethynylphenyl)amino)-3-quinolinecarbonitrile;

h) 4-[(3-ethynylphenyl)amino]-6-nitro-3-quinolinecarbonitrile;

i) N-{4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl}-4-piperidino-2-butynamide;

j) N-{4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl}-4-dipropylamino-2-butynamide;

k) N-{4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl}-2-morpholin-4-ylmethyl-2-propenamide;

l) N-{4-[(3-bromo-4-fluorophenyl)amino]-3-cyano-6-quinolinyl}-4-dimethylamino-2-butenamide;

m) N-{4-[(3-bromo-4-fluorophenyl)amino]-3-cyano-6-quinolinyl}-4-diethylamino-2-butenamide;

n) N-{4-[(3-bromo-4-fluorophenyl)amino]-3-cyano-6-quinolinyl}-4-morpholino-2-butenamide;

o) N-{4-[(3-bromo-4-fluorophenyl)amino]-3-cyano-7-methoxy-6-quinolinyl}-4-morpholino-2-butenamide;

p) 4-[(3-bromophenyl)amino]-7-ethoxy-6-methoxy-3-quinolinecarbonitrile;

q) 7-ethoxy-4-[(3-hydroxy-4-methylphenyl)amino]-6-methoxy-3-quinolinecarbonitrile;

r) N-[4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl]-4-dimethylamino-(z)-2-butenamide;

s) N-[4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl]-4-methoxy-(z)-2-butenamide;

t) 4-[[4[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]amino]-2-methylene-4-oxo-butanoic acid;

u) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-diethylamino-2-butynamide;

v) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-(n-ethylpiperazino)-2-butynamide;

w) N-[4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl]-4-diethylamino-2-butynamide;

x) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-(n-methylpiperazino)-2-butynamide;

y) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-(n-isopropyl-n-methylamino)-2-butynamide;

z) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-diisopropylamino-2-butynamide;

aa) N-[4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl]-4-dimethylamino-2-butynamide;

bb) N-[4-[-(3-chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl]-4-methoxy-2-butynamide;

cc) 4-[(3-bromo-4-fluorophenyl)amino]-6-nitro-3-quinolinecarbonitrile;

dd) 6-amino-4-[(3-bromo-4-fluorophenyl)amino]-3-quinolinecarbonitrile;

ee) N-[4-[(3-bromo-4-fluorophenyl)amino]-3-cyano-6-quinolinyl]-4-dimethylamino-2-butynamide;

ff) 4-diethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide;

gg) 4-morpholin-4-yl-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide;

hh) 4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-6-nitro-quinoline-3-carbonitrile;

ii) 6-amino-4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinoline-3-carbonitrile;

jj) 4-(3-bromo-4-fluoro-phenylamino)-7-methoxy-6-nitro-quinoline-3-carbonitrile;

kk) 6-amino-4-(3-bromo-4-fluoro-phenylamino)-7-methoxy-quinoline-3-carbonitrile;

ll) 4-diethylamino-but-2-enoic acid [4-(3-bromo-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide;

mm) 4-(3-bromo-phenylamino)-7-ethoxy-6-nitro-quinoline-3-carbonitrile;

nn) 6-amino-4-(3-bromo-phenylamino)-7-ethoxy-quinoline-3-carbonitrile;

oo) 4-bromo-but-2-enoic acid [4-(3-bromo-phenylamino)3-cyano-7-ethoxy-quinolin-6-yl]-amide;

pp) 4-morpholin-4-yl-but-2-enoic acid [4(3-bromo-phenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide;

qq) 6-amino-4-(3-bromo-phenylamino)-8-methoxy-quinoline-3-carbonitrile;

rr) 6-amino-4-(3-bromo-phenylamino)-8-methoxy-quinoline-3-carbonitrile;

ss) 4-bromo-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-8-methoxy-quinolin-6-yl]-amide;

tt) 4-dimethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-8-methoxy-quinolin-6-yl]-amide;

uu) 4-diethylamino-but-2-enoic acid [4(3-bromo-phenylamino)-3-cyano-8-methoxy-quinolin-6-yl]-amide;

vv) 4-morpholin-4-yl-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-8-methoxy-quinolin-6-yl]-amide;

ww) 4-dimethylamino-but-2-ynoic acid [4-(3-bromo-phenylamino)-3-cyano-7-methoxy-quinol-6-yl]-amide;

xx) 4-(4-chloro-2-fluoro-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

yy) 4-(3-hydroxy-4-methyl-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

or

zz) 4-(3-dimethylamino-phenylamino)-6,7,8-trimethoxy-quinoline-3-carbonitrile;

or a pharmaceutically acceptable salt thereof.

18. A compound according to claim 1 which is

a) 4-(3-hydroxy-4-methyl-phenylamino)-6,7,8-trimethoxy-quinoline-3-carbonitrile;

b) 4-(4-chloro-2-fluoro-phenylamino)-6,7,8-trimethoxy-quinoline-3-carbonitrile;

c) 4-(4-chloro-2-fluoro-phenylamino)-5,8-dimethoxy-quinoline-3-carbonitrile;

d) 4-(3-hydroxy-4-methyl-phenylamino)-5,8-dimethoxy-quinoline-3-carbonitrile;

e) 4-(3-bromo-phenylamino)-5,8-dimethoxy-quinoline-3-carbonitrile;

f) 4-(3-bromo-phenylamino)-6,7,8-trimethoxy-quinoline-3-carbonitrile;

g) 4-(3-dimethylamino-phenylamino)-5,8-dimethoxy-quinoline-3-carbonitrile;

h) 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-5,8-dimethoxy-quinoline-3-carbonitrile;

i) 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-6,7,8-trimethoxy-quinoline-3-carbonitrile;

j) 4-(3-hydroxy-2-methyl-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

k) 4-(2-hydroxy-6-methyl-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

l) 4-(3-bromo-4-methyl-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

m) 4-(3-chloro-4-hydroxy-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

n) 6,7-dimethoxy-4(2-methylsulfanyl-phenylamino)-quinoline-3-carbonitrile;

o) 1,4-dihydroquinoline-6,7-diethoxy-4oxo-3-carbonitrile;

p) 4-[3-chloro-4-(phenylthio)phenylamino]-6,7-diethoxy-3-quinolinecarbonitrile;

q) 4-[3-chloro-4-(phenylthio)phenylamino]-6,7-dimethoxy-3-quinolinecarbonitrile;

r) 4-(3-chloro-4fluorophenylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

s) 4-(3-acetylphenylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

t) 4-(n-methylphenylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

u) 4-(phenylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

v) 4-(4-fluorophenylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

w) 4-(4-fluoro-2-methylphenylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

x) 4-(3-chlorophenylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

y) 4-(3-fluorophenylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

z) 4-(3-aminophenylamino)-6,7-dimethoxy-3-quinolinecarbonitrile;

aa) 4-(3-acetamidophenylamino)-6,7-dimethoxy-3-quinolinecarbonitrile;

bb) 4-[3-(2-butynoylamino)phenylamino)]-6,7-dimethoxy-3-quinolinecarbonitrile;

cc) 4-[3-(hydroxymethyl)phenylamino]-6,7-dimethoxy-3-quinolinecarbonitrile;

dd) 4-[3-(chloromethyl)phenylamino]-6,7-dimethoxy-3-quinolinecarbonitrile;

ee) 4-[3-(acetylthiomethyl)phenylamino]-6,7-dimethoxy-3-quinolinecarbonitrile;

ff) 4-[3-(thiomethyl)phenylamino]-6,7-dimethoxy-3-quinolinecarbonitrile;

gg) 4-[(3-bromophenyl)amino]-8-methoxy -3-quinolinecarbonitrile;

hh) 4-(4-chloro-2-fluoro-phenylamino)-8-methoxy-quinoline-3-carbonitrile;

ii) 4-(3-hydroxy-4-methyl-phenylamino)-8-methoxy-quinoline-3-carbonitrile;

jj) 4-(3-dimethylamino-phenylamino)-8-methoxy-quinoline-3-carbonitrile;

kk) 4-(4-bromo-3-hydroxy-phenylamino)-8-methoxy-quinoline-3-carbonitrile;

ll) 4-(3-hydroxy-4-methoxy-phenylamino)-8-methoxy-quinoline-3-carbonitrile;

mm) 8-methoxy-4-(2,4,6-trifluoro-phenylamino)-quinoline-3-carbonitrile;

nn) 4-(3-hydroxy-4-methyl-phenylamino)-7-methoxy-quinoline-3-carbonitrile;

oo) 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-methoxy-quinoline-3-carbonitrile;

pp) 4-(4-chloro-2-fluoro-phenylamino)-6-methoxy-quinoline-3-carbonitrile;

qq) 4-(3-hydroxy-4-methyl-phenylamino)-6-methoxy-quinoline-3-carbonitrile;

rr) 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-6-methoxy-quinoline-3-carbonitrile;

ss) 4-(3,5-dichloro-4-hydroxy-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

tt) 4-(2-hydroxy-4-methyl-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

uu) 4-(4hydroxy-3,5-dimethyl-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

vv) 4-(5-chloro-2-hydroxy-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

ww) 4-(3,5-dibromo-4-hydroxy-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

xx) 4-(4-hydroxy-2-methyl-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

yy) 6,7-dimethoxy-4-(pyridin-3-ylamino)-quinoline-3-carbonitrile;

or

zz) 6,7-dimethoxy-4-(3-methylsulfanyl-phenylamino)-quinoline-3-carbonitrile;

or a pharmaceutically acceptable salt thereof.

19. A compound according to claim 1 which is

a) 4-(2-hydroxy-5-methyl-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

b) 4-(2-chloro-4-hydroxy-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

c) 6,7-dimethoxy-4-(4-methylsulfanyl-phenylamino)-quinoline-3-carbonitrile;

d) 4-[4-(2-hydroxy-ethyl)-phenylamino]-6,7-dimethoxy-quinoline-3-carbonitrile;

e) 4-(2,4-dihydroxy-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

f) 4-[2-(2-hydroxy-ethyl)-phenylamino]-6,7-dimethoxy-quinoline-3-carbonitrile;

g) 4-(3-bromophenylamino)-6,7-dihydroxy-3-quinolinecarbonitrile;

h) 4-(3-bromophenylamino)-6,7-di-n-propoxy-3-quinolinecarbonitrile;

i) 4-[(3-bromophenyl)-n-acetylamino]-6,7-dihydroxy-3-quinolinecarbonitrile;

j) 4-(3-bromophenylamino)-6,7-di-n-butoxy-3-quinolinecarbonitrile;

k) 4-(4-chloro-2-fluorophenylamino)-7-methoxy-3-quinolinecarbonitrile;

l) 4-(4-chloro-2-fluorophenylamino)-7-hydroxy-3-quinolinecarbonitrile;

m) 4-[(4-chloro-2-fluorophenylamino)-n-acetylamino]-7-hydroxy-3-quinolinecarbonitrile;

n) 4-(4-chloro-2-fluorophenylamino)-7-ethoxy-3-quinolinecarbonitrile;

o) 4-[(3-bromophenyl)amino]-6,7-bis(2-methoxyethoxy)-3-quinolinecarbonitrile;

p) 4-(2-aminphenylmethylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

q) 4-(3,4-difluorophenylmethylamino)-6,7-diethoxy-3-quinolinecarbonitrile;

r) 4-methoxy-but-2-enoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide;

s) 7-benzyloxy-4-(4-chloro-2-fluoro-phenylamino)-6-methoxy-quinoline-3-carbonitrile;

t) 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-methoxy-6-(3-morpholin-4-yl)-propoxyl-quinoline-3-carbonitrile;

u) N-[4-(3-bromo-phenylamino)-3-cyano-quinolin-6-yl]-3-chloro-(e) acrylamide;

v) N-[4-(3-bromo-phenylamino)-3-cyano-quinolin-6-yl]-3-chloro-(z)-acrylamide;

w) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-morpholino-2-butynamide;

x) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-dimethylamino-2-butynamide;

y) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-t-butyldimethylsiloxy-2-butynamide;

z) N-[4-[(3-bromophenyl)amino]-3-cyano-6-quinolinyl]-4-hydroxy-2-butynamide;

aa) 4-(3-hydroxymethyl-2-methylphenylamino)-6,7-dimethoxyquinoline-3-carbonitrile;

bb) 4-(2-amino-4,5-dimethylphenylamino)-6,7-dimethoxyquinoline-3-carbonitrile;

cc) 4-(4-ethylphenylamino)-6,7-dimethoxyquinoline-3-carbonitrile;

dd) 4-(4-chloro-2-methylphenylamino)-6,7-dimethoxyquinoline-3-carbonitrile;

ee) 6,7-dimethoxy-4-(3-phenoxyphenylamino)quinoline-3-carbonitrile;

ff) 4-(4-chloro-3-trifluoromethylphenylamino)-6,7-dimethoxyquinoline-3-carbonitrile;

gg) 4-(3-hydroxy-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

hh) 4-(4-methyl-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

ii) 4-(3-hydroxy-4-methyl-phenylamino)-8-methoxy-6-nitro-quinoline-3-carbonitrile;

jj) 4-(4-chloro-2-fluoro-phenylamino)-8-methoxy-6-nitro-quinoline-3-carbonitrile;

kk) 4-(3-hydroxy-4-methoxy-phenylamino)-8-methoxy-6-nitro-quinoline-3-carbonitrile;

ll) 6-amino-4-(3-hydroxy-4-methyl-phenylamino)-8-methoxy-quinoline-3-carbonitrile;

mm) 6-amino-4-(3-hydroxy-4-methoxy-phenylamino)-8-methoxy -quinoline-3-carbonitrile;

nn) N-{4-[(3-bromo-4-fluorophenyl)amino]-3-cyano-7-methoxy-6-quinolinyl}-4-bromo-2-butenamide;

oo) N-{4-[(3-bromophenyl)amino]-3-cyano-7-methoxy-6-quinolinyl}-4-chloro-2-butenamide;

pp) N-{3-cyano-4[(3-iodophenyl)amino]-6-quinolinyl}-2-butynamide;

qq) N-{3-cyano-4-[(3-methylphenyl)amino]-6-quinolinyl}-2-propenamide;

rr) N-{4-[(4-bromophenyl)amino]-3-cyano-6-quinolinyl}-2-butynamide;

ss) N-{4-[(3-chloro-4-thiophenoxyphenyl)amino]-3-cyano-6-quinolinyl}-2-propenamide;

tt) N-{3-cyano-4-[(3,4-difluorophenyl)amino]-6-quinolinyl}-2-butynamide;

uu) N-{4-[(3-chlorophenyl)amino]-3-cyano-6-quinolinyl}-2-butynamide;

vv) N-{3-cyano-4-[(3-isopropylphenyl)amino]-6-quinolinyl}-2-butynamide;

ww) N-{3-cyano-4-[(3-isopropylphenyl)amino]-6-quinolinyl}-2-propenamide;

xx) 6-amino-4-[(3-isopropylphenyl)amino]-3-quinolinecarbonitrile;

yy) 4-[(3-isopropylphenyl)amino]-6-nitro-3-quinolinecarbonitrile;

or

zz) 4-(3-bromo-phenylamino)-6-(3-pyrrolidin-1-yl-propylamino)-quinoline-3-carbonitrile;

or a pharmaceutically acceptable salt thereof.

20. A compound according to claim 1 which is

a) 4-(3-azido-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

b) 6-amino-4-[(4-chloro-2-fluorophenyl)amino]-7-methoxy-3-quinolinecarbonitrile;

c) 4-[(4-chloro-2-fluorophenyl)amino]-7-methoxy-6-nitro-3-quinolinecarbonitrile;

d) 4-[(3,4dichlorophenyl)amino]-6-nitro-3-quinolinecarbonitrile;

e) 6-amino-4-[(3-methylsulfanylphenyl)amino]-3-quinolinecarbonitrile;

f) 4-[(3-methylsulfanylphenyl)amino]-6-nitro-3-quinolinecarbonitrile;

g) 4-[(3-trifluoromethoxyphenyl)amino]-6-nitro-3-quinolinecarbonitrile;

h) 4-(3-dimethylamino-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

i) 6,7-dimethoxy-4-(4-methoxy-2-methyl-phenylamino)-quinoline-3-carbonitrile;

j) 4-(3-hydroxy-4-methoxy-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

k) 4-(3-chloro-4-methyl-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

l) 6,7-dimethoxy-4-(4-phenoxy-phenylamino)-quinoline-3-carbonitrile;

m) 4-(5-chloro-2-methoxy-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

n) 3-(3-cyano-6,7-dimethoxy-quinolin-4-ylamino)-2-methyl-benzoic acid;

o) 4-(4-chloro-2-fluoro-phenylamino)-6,7-dihydroxy-quinoline-3-carbonitrile;

p) 4-(3-hydroxy-2-methyl-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

q) 4-(3-chloro-4-methoxy-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile;

r) 6,7-dimethoxy-4-(4-trifluoromethyl-phenylamino)-quinoline-3-carbonitrile;

s) 4-(3,4-dibromophenylamino)-6-nitroquinoline-3-carbonitrile;

t) 6-amino-4-(3-trifluoromethylphenylamino)quinoline-3-carbonitrile;

u) 6-amino-4-(3,4-dibromophenylamino)quinoline-3-carbonitrile;

v) N-[3-cyano-4-(3,4-dibromophenylamino)quinolin-6-yl]acrylamide;

w) N-[4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]propionamide;

x) (e)-but-2-enoic acid [4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]amide;

y) N-[4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]-2-methylacrylamide;

z) 4-(3-fluorophenylamino)-6-nitroquinoline-3-carbonitrile;

aa) 6-amino-4-(3-fluorophenylamino)quinoline-3-carbonitrile;

bb) 4(3-dimethylaminophenylamino)-6-nitroquinoline-3-carbonitrile;

cc) 4-(4-dimethylaminophenylamino)-6-nitroquinoline-3-carbonitrile;

dd) 6-amino-4-(3-dimethylaminophenylaminoquinoline-3-carbonitrile;

ee) 6-amino-4-(4-dimethylaminophenylamino)quinoline-3-carbonitrile;

ff) but-2-ynoic acid [4-(3-fluorophenylamino)-3-cyanoquinolin-6-yl]amide;

gg) N-[3-cyano-4-(3-dimethylaminophenylamino)quinolin-6-yl]acrylamide;

hh) N-[3-cyano-4-(4-dimethylaminophenylamino)quinolin-6-yl]acrylamide;

ii) but-2-ynoic acid [3-cyano-4-(3-dimethylaminophenylamino)quinolin-6-yl]amide;

jj) but-2-ynoic acid [3-cyano-4-(4dimethylaminophenylamino)quinolin-6-yl]amide;

kk) 4-(3-bromophenylamino)-6-dimethylaminoquinoline-3-carbonitrile hydrochloride;

ll) 6-dimethylamino-4-(3-methoxyphenylamino)quinoline-3-carbonitrile hydrochloride;

mm) 2-bromo-n-[4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]acetamide;

nn) 6-iodo-4-(3-methoxyphenylamino)quinoline-3-carbonitrile;

oo) 4-(4-hydroxy-2-methyl-phenylamino)-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrile;

pp) 4-(3-bromo-phenylamino)-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrile;

qq) 6-methoxy-4-(2-methylsulfanyl-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrile;

or

rr) 4-(4-hydroxy-3,5-dimethyl-phenylamino)-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline-3-carbonitrile;

or a pharmaceutically acceptable salt thereof.

21. A method of inhibiting the biological effects of a deregulated protein kinase in a mammal which comprises administering to said mammal an effective amount of a compound having the formula ##STR22## 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, and benzoylamino;

n is 0-1;

Y is --NH--, --O--, --S--, or --NR--,

R is alkyl of 1-6 carbon atoms;

R₁, R₂, R₃, and R₄ are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, 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, aminoalkyl of 1-4 carbon atoms, N-alkylaminoalkyl of 2-7 carbon atoms, N,N-dialkylaminoalkyl of 3-14 carbon atoms, phenylamino, benzylamino, ##STR23## R₅ is alkyl of 1-6 carbon atoms, alkyl optionally substituted with one or more halogen atoms, phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, nitro, cyano, or alkyl of 1-6 carbon atoms groups;

R₆ is hydrogen, alkyl of 1-6 carbon atoms, or alkenyl of 2-6 carbon atoms;

R₇ is chloro or bromo

R₈ is hydrogen, alkyl of 1-6 carbon atoms, aminoalkyl of 1-6 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-12 carbon atoms, N-cycloalkylaminoalkyl of 4-12 carbon atoms, N-cycloalkyl-N-alkylaminoalkyl of 5-18 carbon atoms, N,N-dicycloalkylaminoalkyl of 7-18 carbon atoms, 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, azacycloalkyl-N-alkyl of 3-11 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-8 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, chloro, fluoro, or bromo;

Z is amino, hydroxy, alkoxy of 1-6 carbon atoms, alkylamino wherein the alkyl moiety is of 1-6 carbon atoms, dialkylamino wherein each of the alkyl moieties is of 1-6 carbon atoms, morpholino, piperazino, N-alkylpiperazino wherein the alkyl moiety is of 1-6 carbon atoms, or pyrrolidino;

m=1-4,q=1-3,and p=0-3;

any of the substituents R₁, R₂, R₃, or R₄ that are located on contiguous carbon atoms can together be the divalent radical --O--C(R₈)₂ --O--;

or a pharmaceutically acceptable salt thereof with the proviso that when Y is --NH--, R₁, R₂, R₃, and R₄ are hydrogen, and n is 0, X is not 2-methylphenyl.

22. 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 having the formula ##STR24## 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, and benzoylamino;

n is 0-1;

Y is --NH--, --O--, --S--, or --NR--;

R is alkyl of 1-6 carbon atoms;

R₁, R₂, R₃, and R₄ are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, 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, aminoalkyl of 1-4 carbon atoms, N-alkylaminoalkyl of 2-7 carbon atoms, N,N-dialkylaminoalkyl of 3-14 carbon atoms, phenylamino, benzylamino, ##STR25## R₅ is alkyl of 1-6 carbon atoms, alkyl optionally substituted with one or more halogen atoms, phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, nitro, cyano, or alkyl of 1-6 carbon atoms groups;

R₆ is hydrogen, alkyl of 1-6 carbon atoms, or alkenyl of 2-6 carbon atoms;

R₇ is chloro or bromo

R₈ is hydrogen, alkyl of 1-6 carbon atoms, aminoalkyl of 1-6 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-12 carbon atoms, N-cycloalkylaminoalkyl of 4-12 carbon atoms, N-cycloalkyl-N-alkylaminoalkyl of 5-18 carbon atoms, N,N-dicycloalkylaminoalkyl of 7-18 carbon atoms, 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, azacycloalkyl-N-alkyl of 3-11 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-8 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, chloro, fluoro, or bromo;

Z is amino, hydroxy, alkoxy of 1-6 carbon atoms, alkylamino wherein the alkyl moiety is of 1-6 carbon atoms, dialkylamino wherein each of the alkyl moieties is of 1-6 carbon atoms, morpholino, piperazino, N-alkylpiperazino wherein the alkyl moiety is of 1-6 carbon atoms, or pyrrolidino;

m=1-4, q=1-3, and p=0-3;

any of the substituents R₁, R₂, R₃, or R₄ that are located on contiguous carbon atoms can together be the divalent radical --O--C(R₈)₂ --O--;

or a pharmaceutically acceptable salt thereof with the proviso that when Y is --NH--, R₁, R₂, R₃, and R₄ are hydrogen, and n is 0, X is not 2-methylphenyl.

23. The method according to claim 22 wherein the neoplasm expresses EGFR.

24. The method according to claim 22 wherein the neoplasm expresses MAPK.

25. The method according to claim 22 wherein the neoplasm expresses ECK.

26. The method according to claim 22 wherein the neoplasm expresses KDR.

27. The method according to claim 22 wherein the neoplasm is selected from the group consisting of breast, kidney, bladder, mouth, larynx, esophagus, stomach, colon, ovary, and lung.

28. A method of treating, inhibiting the progression of, or eradicating polycystic kidney disease in a mammal which comprises administering to said mammal an effective amount of a compound having the formula ##STR26## 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, and benzoylamino;

n is 0-1;

Y is --NH--, --O--, --S--, or --NR--;

R is alkyl of 1-6 carbon atoms;

R₁, R₂, R₃, and R₄ are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, 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, aminoalkyl of 1-4 carbon atoms, N-alkylaminoalkyl of 2-7 carbon atoms, N,N-dialkylaminoalkyl of 3-14 carbon atoms, phenylamino, benzylamino, ##STR27## R₅ is alkyl of 1-6 carbon atoms, alkyl optionally substituted with one or more halogen atoms, phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, nitro, cyano, or alkyl of 1-6 carbon atoms groups;

R₆ is hydrogen, alkyl of 1-6 carbon atoms, or alkenyl of 2-6 carbon atoms;

R₇ is chloro or bromo

R₈ is hydrogen, alkyl of 1-6 carbon atoms, aminoalkyl of 1-6 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-12 carbon atoms, N-cycloalkylaminoalkyl of 4-12 carbon atoms, N-cycloalkyl-N-alkylaminoalkyl of 5-18 carbon atoms, N,N-dicycloalkylaminoalkyl of 7-18 carbon atoms, 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, azacycloalkyl-N-alkyl of 3-11 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-8 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, chloro, fluoro, or bromo;

Z is amino, hydroxy, alkoxy of 1-6 carbon atoms, alkylamino wherein the alkyl moiety is of 1-6 carbon atoms, dialkylamino wherein each of the alkyl moieties is of 1-6 carbon atoms, morpholino, piperazino, N-alkylpiperazino wherein the alkyl moiety is of 1-6 carbon atoms, or pyrrolidino;

m=1-4,q=1-3,and p=0-3;

any of the substituents R₁, R₂, R₃, or R₄ that are located on contiguous carbon atoms can together be the divalent radical --O--C(R₈)₂ --O--;

or a pharmaceutically acceptable salt thereof with the proviso that when Y is --NH--, R₁, R₂, R₃, and R₄ are hydrogen, and n is 0, X is not 2-methylphenyl.

29. A pharmaceutical composition which comprises a compound having the formula ##STR28## 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, and benzoylamino;

n is 0-1;

Y is --NH--, --O--, --S--, or --NR--;

R is alkyl of 1-6 carbon atoms;

R₁, R₂, R₃, and R₄ are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, 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, aminoalkyl of 1-4 carbon atoms, N-alkylaminoalkyl of 2-7 carbon atoms, N,N-dialkylaminoalkyl of 3-14 carbon atoms, phenylamino, benzylamino, ##STR29## R₅ is alkyl of 1-6 carbon atoms, alkyl optionally substituted with one or more halogen atoms, phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, nitro, cyano, or alkyl of 1-6 carbon atoms groups;

R₆ is hydrogen, alkyl of 1-6 carbon atoms, or alkenyl of 2-6 carbon atoms;

R₇ is chloro or bromo

R₈ is hydrogen, alkyl of 1-6 carbon atoms, aminoalkyl of 1-6 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-12 carbon atoms, N-cycloalkylaminoalkyl of 4-12 carbon atoms, N-cycloalkyl-N-alkylaminoalkyl of 5-18 carbon atoms, N,N-dicycloalkylaminoalkyl of 7-18 carbon atoms, 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, azacycloalkyl-N-alkyl of 3-11 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-8 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, chloro, fluoro, or bromo;

Z is amino, hydroxy, alkoxy of 1-6 carbon atoms, alkylamino wherein the alkyl moiety is of 1-6 carbon atoms, dialkylamino wherein each of the alkyl moieties is of 1-6 carbon atoms, morpholino, piperazino, N-alkylpiperazino wherein the alkyl moiety is of 1-6 carbon atoms, or pyrrolidino;

m=1-4,q=1-3,and p=0-3;

any of the substituents R₁, R₂, R₃, or R₄ that are located on contiguous carbon atoms can together be the divalent radical --O--C(R₈)₂ --O--;

or a pharmaceutically acceptable salt thereof with the proviso that when Y is --NH--, R₁, R₂, R₃, and R₄ are hydrogen, and n is 0, X is not 2-methylphenyl and a pharmaceutically acceptable carrier.