US2003087881A1PendingUtilityA1
Irreversible inhibitors of tyrosine kinases
Priority: Jul 29, 1997Filed: Oct 17, 2002Published: May 8, 2003
Est. expiryJul 29, 2017(expired)· nominal 20-yr term from priority
Inventors:Alexander James Bridges
C07D 495/04C07D 403/04C07D 401/04C07D 471/04C07D 487/04
48
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Claims
Abstract
The present invention provides compounds that are irreversible inhibitors of tyrosine kinases. Also provided is a method of treating cancer, restenosis, atherosclerosis, endometriosis, and psoriasis and a pharmaceutical composition that comprises a compound that is an irreversible inhibitor of tyrosine kinases.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound having the Formula I
wherein X is -D-E-F and Y is —SR 4 , halogen, —OR 4 , —NHR 3 or hydrogen, or X is —SR 4 , halogen, —OR 4 , —NHR 3 or hydrogen, and Y is -D-E-F;
each R a is independently hydroxy, amino. N-mono- or N,N-di-(C 1 -C 4 ) alkylamino, sulfo, or (C 1 -C 4 )alkoxy (provided that such groups are not attached to a ring carbon which is adjacent to an oxy, thio, or —N—), or R a is independently carboxy, hydroxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy(C 1 -C 4 ) alkyl, amino(C 1 -C 4 )alkyl, mono-N— or di-N,N-(C 1 -C 4 ) alkylamino(C 1 -C 4 )alkyl, morpholino(C 1 -C 4 )alkyl, 4-(C 1 -C 4 )alkyl-piperazin-1-yl(C 1 -C 4 )alkyl, carboxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxycarbonyl, sulfo(C 1 -C 4 )alkyl or (C 1 -C 4 )alkyl;
each R b is independently mono-, di-, or trifluoromethyl, halo, nitro, hydroxy, amino, axido, isothiocyano, (C 1 -C 4 )alkyl, phenyl, thienyl, (C 1 -C 4 )alkoxy, benzyloxy, phenoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 4 )alkylenedioxy, cyano, benzoylamino, trifluoromethylcarbonylamino, (C 1 -C 4 )alkanoylamino, (C 1 -C 4 )alkanoyl, N-mono- or N,N-di-(C 1 -C 4 )alkylamino, (C 1 -C 4 )alkylsulfonylamino, trifluoromethylsulfonylamino, (C 1 -C 4 )alkylthio, (C 1 -C 4 )alkylsulfinyl or (C 1 -C 4 )alkylsulfonyl, pyrrol-1-yl, piperidin-1-yl or pyrrolidin-1-yl, said phenyl, benzyloxy, phenoxy, and benzoylamino optionally monosubstituted with halo, nitro, trifluoromethyl, hydroxy, or (C 1 -C 4 )alkyl and said (C 1 -C 4 )alkylenedioxy is linked at both ends to adjacent carbons on the benzene moiety, or R b is -Z a R 77 ;
J is —CH 2 —, thio, —N(H)—, or oxy;
g is 0, 1, or2;
h is 0 to4;
k is 0, 1, or 2;
S completes a 5- or 6-membered aromatic or partially saturated ring that can contain an oxygen or sulfur atom;
T is —CH 2 , —N(H)—, thio, or oxy;
S a is —CH 2 —, oxy, or thio;
A 1 completes a 7- to 9-membered mono-unsaturated mono-aza ring;
Q a is a 9- or 10-membered bicyclic heterocyclic moiety, or a hydrogenated derivative thereof, containing one or two nitrogen heteroatoms and optionally containing a further heteroatom selected from nitrogen, oxygen and sulfur, or Q a is a 9- or 10-membered bicyclic aryl moiety, or a hydrogenated derivative thereof, which heterocyclic or aryl moiety, or hydrogenated derivatives thereof, may optionally bear one or two substituents selected from halogen, hydroxy, oxo, amino, nitro, carbamoyl, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkylamino, di-[(C 1 -C 4 )alkyl]amino, and (C 2 -C 4 )alkanoyl amino;
R 1 is hydrogen, halogen, or C 1 -C 6 alkyl;
R 2 , R 3 , and R 4 are independently hydrogen, C 1 -C 6 alkyl, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1 piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n -imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —(CH 2 ) n —N-hexahydroazepine or substituted C 1 -C 6 alkyl, wherein the substituents are selected from —OH, NH 2 , or
A and B are independently hydrogen, C 1 -C 6 alkyl, —(CH 2 ) n OH, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1 -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n —N-pyridyl, —(CH 2 ) n -imidazoyl, or —(CH 2 ) n —N-imidazoyl;
Z 1 , Z 2 , or Z 3 are independently hydrogen, halogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 alkoxy, C 3 -C 8 cycloalkoxy, nitro, C 1 -C 6 perfluoroalkyl, hydroxy, C 1 -C 6 acyloxy, —NH 2 , —NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl) 2 , —NH(C 3 -C 8 cycloalkyl), —N(C 3 -C 8 cycloalkyl) 2 , hydroxymethyl, C 1 -C 6 acyl, cyano, azido, C 1 -C 6 thioalkyl, C 1 -C 6 sulfinylalkyl, C 1 -C 6 sulfonylalkyl, C 3 -C 8 thiocycloalkyl, C 3 -C 8 sulfinylcycloalkyl, C 3 -C 8 sulfonylcycloalkyl, mercapto, C 1 -C 6 alkoxycarbonyl, C 3 -C 8 cycloalkoxycarbonyl, C 2 -C 4 alkenyl, C 4 -C 8 cycloalkenyl, or C 2 -C 4 alkynyl;
Z a is a bond, —CH 2 —, —S—, SO 2 , —NH—, —O—, —OCH 2 —, —S—CH 2 —, —SO 2 —, or —CH 2 CH 2 —;
R 77 is phenyl, substituted phenyl, or a 5- to 10-membered optionally substituted heterocyclic aromatic ring;
R 5 is hydrogen, halogen, C 1 -C 6 perfluoroalkyl, 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n -piperazinyl, —(CH 2 ) n -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 )n—N-imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino,
—CH═CH—(C 1 -C 6 )alkyl, —(CH 2 ) n —N-hexahydroazepine, —(CH 2 ) n NH 2 ,—(CH 2 ) n NH (C 1 -C 6 alkyl), —(CH 2 ) n N(C 1 -C 6 alkyl) 2 , -1-oxo(C 1 -C 6 )alkyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, N—(C 1 -C 6 )alkylcarbamoyl, phenyl or substituted phenyl, wherein the substituted phenyl can have from one to three substituents independently selected from Z 1 , Z 2 , Z 3 or a monocyclic heteroaryl group, and each C 1 -C 6 alkyl group can be substituted with —OH, —NH 2 or —NAB, where A and B are as defined above; and
n is 1 to 4, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.
2 . A compound of claim 1 wherein
and Y is hydrogen, or X is hydrogen, and Y
3 . A compound of claim 1 wherein Y is -D-E-F and -D-E-F is
4 . A compound of claim 1 wherein X is -D-E-F and -D-E-F is
5 . A compound of claim 3 wherein R 2 is hydrogen.
6 . A compound of claim 4 wherein R 2 is hydrogen.
7 . A compound of claim 3 wherein R 2 is —(CH 2 ) n -morpholino.
8 . A compound of claim 4 wherein R 2 is —(CH 2 ) n -morpholino.
9 . A compound of claim 3 wherein R 5 is carboxy, (C 1 -C 6 )alkyloxycarbonyl or C 1 -C 6 alkyl.
10 . A compound of claim 1 wherein Y is -D-E-F, and X is —O—(CH 2 ) n -morpholino.
11 . A compound of claim 1 wherein Y is -D-E-F, and X is —O—(CH 2 ) n —N 1 -piperazinyl[N 4 —(C 1 -C 6 )alkyl].
12 . A compound of claim I wherein Y is -D-E-F and X is —O—(CH 2 ) n -imidazoyl.
13 . A compound having the Formula II
Q-Z II
wherein Q is
X is -D-E-F and Y is —SR 4 , —OR 4 , —NHR 3 or hydrogen, or X is —SR 4 , —OR 4 , —NHR 3 or hydrogen, and Y is -D-E-F;
each R a is independently hydroxy, amino, N-mono- or N,N-di-(C 1 -C 4 ) alkylamino, sulfo, or (C 1 -C 4 )alkoxy (provided that such groups are not attached to a ring carbon which is adjacent to an oxy, thio, or —N—), or R a is independently carboxy, hydroxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy(C 1 -C 4 ) alkyl, amino(C 1 -C 4 )alkyl, mono-N— or di-N,N—(C 1 -C 4 ) alkylamino(C 1 -C 4 )alkyl, morpholino(C 1 -C 4 )alkyl, 4-(C 1 -C 4 )alkyl-piperazin-1-yl(C 1-4 )alkyl, carboxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxycarbonyl, sulfo(C 1 -C 4 )alkyl or (C 1 -C 4 )alkyl;
each R b is independently mono-, di-, or trifluoromethyl, halo, nitro, hydroxy, amino, axido, isothiocyano, (C 1 -C 4 )alkyl, phenyl, thienyl, (C 1 -C 4 )alkoxy, benzyloxy, phenoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 4 )alkylenedioxy, cyano, benzoylamino, trifluoromethylcarbonylamino, (C 1 -C 4 )alkanoylamino, (C 1 -C 4 )alkanoyl, N-mono- or N,N-di-(C 1 -C 4 )alkylamino, (C 1 -C 4 )alkylsulfonylamino, trifluoromethylsulfonylamino, (C 1 -C 4 )alkylthio, (C 1 -C 4 )alkylsulfinyl or (C 1 -C 4 )alkylsulfonyl, pyrrol-1-yl, piperidin-1-yl or pyrrolidin-1-yl, said phenyl, benzyloxy, phenoxy, and benzoylamino optionally monosubstituted with halo, nitro, trifluoromethyl, hydroxy, or (C 1 -C 4 )alkyl and said (C 1 -C 4 )alkylenedioxy is linked at both ends to adjacent carbons on the benzene moiety, or R b is -Z a R 77 ;
J is —CH 2 —, thio, —N(H)—, or oxy;
g is 0, 1, or2;
h is 0 to 4;
k is 0, 1, or 2;
S completes a 5- or 6-membered aromatic or partially saturated ring that can contain an oxygen or sulfur atom:
T is —CH 2 , —N(H)—, thio, or oxy;
S a is —CH 2 —, oxy, or thio;
A 1 completes a 7- to 9-membered mono-unsaturated mono-aza ring;
Q a is a 9- or 10-membered bicyclic heterocyclic moiety, or a hydrogenated derivative thereof, containing one or two nitrogen heteroatoms and optionally containing a further heteroatom selected from nitrogen, oxygen and sulfur, or Q a is a 9- or 10-membered bicyclic aryl moiety, or a hydrogenated derivative thereof, which heterocyclic or aryl moiety, or hydrogenated derivatives thereof, may optionally bear one or two substituents selected from halogen, hydroxy, oxo, amino, nitro, carbamoyl, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkylamino, di-[(C 1 -C 4 )alkyl]amino, and (C 2 -C 4 )alkanoylamino;
R 1 is hydrogen, halogen, or C 1 -C 6 alkyl;
R 2 , R 3 , and R 4 are independently hydrogen, C 1 -C 6 alkyl, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1 piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n -imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —(CH 2 ) n —N-hexahydroazepine or substituted C 1 -C 6 alkyl, wherein the substituents are selected from —OH NH 2 , or
A and B are independently hydrogen, C 1 -C 6 alkyl, —(CH 2 ) n OH, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1 -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl. —(CH 2 ) n —N-pyridyl, —(CH 2 ) n -imidazoyl, or —(CH 2 ) n —N-imidazoyl:
E 1 , E 2 , or E 3 are independently hydrogen, halogen. C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 alkoxy, C 3 -C 8 cycloalkoxy, nitro, C 1 -C 6 perfluoroalkyl, hydroxy, C 1 -C 6 acyloxy, —NH 2 , —NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl) 2 , —NH(C 3 -C 8 cycloalkyl), —N(C 3 -C 8 cycloalkyl) 2 , hydroxymethyl, C 1 -C 6 acyl, cyano, azido, C 1 -C 6 thioalkyl, C 1 -C 6 sulfinylalkyl, C 1 -C 6 sulfonylalkyl, C 3 -C 8 thiocycloalkyl, C 3 -C 8 sulfinylcycloalkyl, C 3 -C 8 sulfonylcycloalkyl, mercapto, C 1 -C 6 alkoxycarbonyl, C 3 -C 8 cycloalkoxycarbonyl, C 2 -C 4 alkenyl, C 4 -C 8 cycloalkenyl, or C 2 -C 4 alkynyl;
Z a is a bond, —CH 2 —, —S—, SO 2 , —NH—, —O—, —OCH 2 —, —S—CH 2 —, —SO 2 —, or —CH 2 CH 2 —;
R 77 is phenyl, substituted phenyl, or a 5- to 10-membered optionally substituted heterocyclic aromatic ring;
R 5 is hydrogen, halogen, C 1 -C 6 perfluoroalkyl, 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n -piperazinyl, —(CH 2 ) n -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 )n-N-imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino,
—CH═CH—(C 1 -C 6 )alkyl, —(CH 2 ) n —N-hexahydroazepine, —(CH 2 ) n NH 2 ,—(CH 2 ) n NH (C 1 -C 6 alkyl), —(CH 2 ) n N(C 1 -C 6 alkyl) 2 , -1-oxo(C 1 -C 6 )alkyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, N—(C 1 -C 6 )alkylcarbamoyl, phenyl or substituted phenyl, wherein the substituted phenyl can have from one to three substituents independently selected from E 1 , E 2 , E 3 or a monocyclic heteroaryl group, and each C 1 -C 6 alkyl group can be substituted with —OH, —NH 2 or —NAB, where A and B are as defined above; and
n is 1 to 4, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.
14 . A compound of claim 13 wherein Q is
15 . A compound of claim 13 wherein Q is
16 . A compound of claim 13 wherein Q is
17 . A compound of claim 13 wherein Q is
18 . A compound of claim 15 wherein X is
19 . A compound of claim 16 wherein X is
20 . A compound of claim 16 wherein X is
21 . A compound of claim 14 wherein X is
and Y is hydrogen.
22 . A compound having the Formula II
Q-Z II
wherein Q is
X is -D-E-F and Y is —SR 4 , —OR 4 , —NHR 3 or hydrogen, or X is —SR 4 , —OR 4 , —NHR 3 or hydrogen, and Y is -D-E-F;
each R a is independently hydroxy, amino, N-mono- or N,N-di-(C 1— C 4 ) alkylamino, sulfo, or (C 1 -C 4 )alkoxy (provided that such groups are not attached to a ring carbon which is adjacent to an oxy, thio, or —N—), or R a is independently carboxy, hydroxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy(C 1 -C 4 ) alkyl, amino(C 1 -C 4 )alkyl, mono-N— or di-N,N—(C 1 -C 4 ) alkylamino(C 1 -C 4 )alkyl, morpholino(C 1 -C 4 )alkyl, 4-(C 1 -C 4 )alkyl-piperazin-1-yl(C 1— C 4 )alkyl, carboxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxycarbonyl, sulfo(C 1 -C 4 )alkyl or (C 1 -C 4 )alkyl;
each R b is independently mono-, di-, or trifluoromethyl, halo, nitro, hydroxy, amino, axido, isothiocyano, (C 1 -C 4 )alkyl, phenyl, thienyl, (C 1 -C 4 )alkoxy, benzyloxy, phenoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 4 )alkylenedioxy, cyano, benzoylamino, trifluoromethylcarbonylamino. (C 1 -C 4 )alkanoylamino, (C 1 -C 4 )alkanoyl, N-mono- or N,N-di-(C 1 -C 4 )alkylamino, (C 1 -C 4 )alkylsulfonylamino, trifluoromethylsulfonylamino, (C 1— C 4 )alkylthio, (C 1 -C 4 )alkylsulfinyl or (C 1 -C 4 )alkylsulfonyl, pyrrol-1-yl, piperidin-1-yl or pyrrolidin-1-yl, said phenyl, benzyloxy, phenoxy, and benzoylamino optionally monosubstituted with halo, nitro, trifluoromethyl, hydroxy, or (C 1 -C 4 )alkyl and said (C 1 -C 4 )alkylenedioxy is linked at both ends to adjacent carbons on the benzene moiety, or R b is -Z a R 77 ;
J is —CH 2 —, thio, —N(H)—, or oxy;
g is 0, 1, or 2;
h is 0 to 4;
k is 0, 1, or 2;
S completes a 5- or 6-membered aromatic or partially saturated ring that can contain an oxygen or sulfur atom;
T is —CH 2 , —N(H)—, thio, or oxy;
S a is —CH 2 —, oxy, or thio;
A 1 completes a 7- to 9-membered mono-unsaturated mono-aza ring;
Q a is a 9- or 10-membered bicyclic heterocyclic moiety, or a hydrogenated derivative thereof, containing one or two nitrogen heteroatoms and optionally containing a further heteroatom selected from nitrogen, oxygen and sulfur, or Q a is a 9- or 10-membered bicyclic aryl moiety, or a hydrogenated derivative thereof, which heterocyclic or aryl moiety, or hydrogenated derivatives thereof, may optionally bear one or two substituents selected from halogen, hydroxy, oxo, amino, nitro, carbamoyl, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkylamino, di-[(C 1 -C 4 )alkyl]amino, and (C 2 -C 4 )alkanoylamino;
R 1 is hydrogen, halogen, or C 1 -C 6 alkyl;
R 2 , R 3 , and R 4 are independently hydrogen, C 1 -C 6 alkyl. —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl. —(CH 2 ) n —N 1 piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n -imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —(CH 2 ) n —N-hexahydroazepine or substituted C 1 -C 6 alkyl, wherein the substituents are selected from —OH, —NH 2 , or
A and B are independently hydrogen, C 1 -C 6 alkyl, —(CH 2 ) n OH, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1 -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n —N-pyridyl, —(CH 2 ) n -imidazoyl, or —(CH 2 ) n —N-imidazoyl;
E 1 , E 2 , or E 3 are independently hydrogen, halogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 alkoxy, C 3 -C 8 cycloalkoxy, nitro, C 1 -C 6 perfluoroalkyl, hydroxy, C 1 -C 6 acyloxy, —NH 2 , —NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl) 2 , —NH(C 3 -C 8 cycloalkyl), —N(C 3 -C 8 cycloalkyl) 2 , hydroxymethyl, C 1 -C 6 acyl, cyano, azido, C 1 -C 6 thioalkyl, C 1 -C 6 sulfinylalkyl, C 1 -C 6 sulfonylalkyl, C 3 -C 8 thiocycloalkyl, C 3 -C 8 sulfinylcycloalkyl, C 3 -C 8 sulfonylcycloalkyl, mercapto, C 1 -C 6 alkoxycarbonyl, C 3 -C 8 cycloalkoxycarbonyl, C 2 -C 4 alkenyl, C 4 -C 8 cycloalkenyl, or C 2 -C 4 alkynyl;
Z a is a bond, —CH 2 —, —S—, SO 2 , —NH—, —O—, —OCH 2 -, -S—CH 2 —, —SO 2 —, or —CH 2 CH 2 —;
R 77 is phenyl, substituted phenyl, or a 5- to 10-membered optionally substituted heterocyclic aromatic ring;
R 5 is hydrogen, halogen, C 1 -C 6 perfluoroalkyl, 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n -piperazinyl, —(CH 2 ) n -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 )n-N-imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino,
—CH═CH—(C 1 -C 6 )alkyl, —(CH 2 ) n —N-hexahydroazepine, —(CH 2 ) n NH 2 ,—(CH 2 ) n NH (C 1 -C 6 alkyl), —(CH 2 ) n N(C 1 -C 6 alkyl) 2 , -1-oxo(C 1 -C 6 )alkyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, N—(C 1 -C 6 )alkylcarbamoyl, phenyl or substituted phenyl, wherein the substituted phenyl can have from one to three substituents independently selected from E 1 , E 2 , E 3 or a monocyclic heteroaryl group, and each C 1 -C 6 alkyl group can be substituted with —OH, —NH 2 or —NAB, where A and B are as defined above; and
n is 1 to 4, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.
23 . A compound of claim 22 wherein Q is
24 . A compound of claim 22 wherein Q is
25 . A compound of claim 23 wherein X is
26 . A compound of claim 24 wherein X is
27 . A pharmaceutically acceptable composition that comprises a compound of claim 1 .
28 . A pharmaceutically acceptable composition that comprises a compound of claim 13 .
29 . A pharmaceutically acceptable composition that comprises a compound of claim 22 .
30 . A method of treating cancer, the method comprising administering to a patient having cancer a therapeutically effective amount of a compound of claim 1 .
31 . A method of treating or preventing restenosis, the method comprising administering to a patient having restenosis or at risk of having restenosis a therapeutically effective amount of a compound of claim 1 .
32 . A method of treating cancer, the method comprising administering to a patient having cancer a therapeutically effective amount of a compound of claim 13 .
33 . A method of treating or preventing restenosis, the method comprising administering to a patient having restenosis or at risk of having restenosis a therapeutically effective amount of a compound of claim 13 .
34 . A method of treating cancer, the method comprising administering to a patient having cancer a therapeutically effective amount of a compound of claim 22 .
35 . A method of treating or preventing restenosis, the method comprising 5administering to a patient having restenosis or at risk of having restenosis, a therapeutically effective amount of a compound of claim 22 .
36 . A method of irreversibly inhibiting tyrosine kinases, the method comprising administering to a patient a tyrosine kinase inhibition a tyrosine kinase inhibiting amount of a compound of claim 1 .
37 . A method of irreversibly inhibiting tyrosine kinases, the method comprising administering to a patient in need of tyrosine kinase inhibition a amount of tyrosine kinase inhibiting amount of a compound of claim 13 .
38 . A method of irreversibly inhibiting tyrosine kinases, the method comprising administering to a patient in need of tyrosine kinase inhibition a tyrosine kinase inhibiting amount of a compound of claim 22 .
39 . A method of treating psoriasis, the method comprising administering to a patient having psoriasis a therapeutically effective amount of a compound of claim 1 .
40 . A method of treating psoriasis, the method comprising administering to a patient having psoriasis a therapeutically effective amount of a compound of claim 13 .
41 . A method of treating psoriasis, the method comprising administering to a patient having psoriasis a therapeutically effective amount of a compound of claim 22 .
42 . A method of treating atherosclerosis, the method comprising administering to a patient having atherosclerosis a therapeutically effective amount of a compound of claim 1 .
43 . A method of treating atherosclerosis, the method comprising administering to a patient having atherosclerosis a therapeutically effective amount of a compound of claim 13 .
44 . A method of treating atherosclerosis, the method comprising administering to a patient having atherosclerosis a therapeutically effective amount of a compound of claim 22 .
45 . A method of treating endometriosis, the method comprising administering to a patient having endometriosis a therapeutically effective amount of a compound of claim 1 .
46 . A method of treating endometriosis, the method comprising administering to a patient having endometriosis a therapeutically effective amount of a compound of claim 13 .
47 . A method of treating endometriosis, the method comprising administering to a patient having endometriosis a therapeutically effective amount of a compound of claim 22 .
48 . A compound according to claim 1 wherein X is -D-E-F and F is
and R 5 is 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n -piperazinyl, —(CH 2 ) n -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH2) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —CH═CH—(C 1 -C 6 )alkyl, —(CH 2 ) n —N-hexahydroazepine, —(CH 2 ) n NH 2 ,—(CH 2 ) n NH(C 1 -C 6 alkyl), —(CH 2 ) n N(C 1 -C 6 alkyl) 2 , -1-oxo(C 1 -C 6 )alkyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, N—(C 1 -C 6 )alkylcarbamoyl, and each C 1 -C 1 alkyl group of 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —CH═CH—(C 1 -C 6 )alkyl, -1-oxo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyloxycarbonyl, or —N—(C 1 -C 6 )alkylcarbamoyl is substituted with —OH, —NH 2 , or —NAB, where A and B are as defined above; or
Y is -D-E-F and F is
and R 5 is 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n -piperazinyl, —(CH 2 ) n -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH2) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —CH═CH—(C 1 -C 6 )alkyl, —(CH 2 ) n —N-hexahydroazepine, —(CH 2 ) n NH 2 ,—(CH 2 ) n NH(C 1 -C 6 alkyl), —(CH 2 ) n N(C 1 -C 6 alkyl) 2 , -1-oxo(C 1 -C 6 )alkyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, N—(C 1 -C 6 )alkylcarbamoyl, and each C 1 -C 1 alkyl group of 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —CH═CH—(C 1 -C 6 )alkyl, -1-oxo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyloxycarbonyl, or —N—(C 1 -C 6 )alkylcarbamoyl is substituted with —OH, —NH 2 , or —NAB, where A and B are as defined above.
49 . A compound according to claim 13 wherein X is -D-E-F and F is
and R 5 is 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n -piperazinyl, —(CH 2 ) n -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —CH═CH—(C 1 -C 6 )alkyl, —(CH 2 ) n —N-hexahydroazepine, —(CH 2 ) n NH 2 ,—(CH 2 ) n NH(C 1 -C 6 alkyl), —(CH 2 ) n N(C 1 -C 6 alkyl) 2 , -1-oxo(C 1 -C 6 )alkyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, N—(C 1 -C 6 )alkylcarbamoyl, and each C 1 -C 1 alkyl group of 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —CH═CH—(C 1 -C 6 )alkyl, -1-oxo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyloxycarbonyl, or —N—(C 1 -C 6 )alkylcarbamoyl is substituted with —OH, —NH 2 , or —NAB, where A and B are as defined above; or
Y is -D-E-F and F is
and R 5 is 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n -piperazinyl, —(CH 2 ) n -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH2) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —CH═CH—(C 1 -C 6 )alkyl, —(CH 2 ) n —N-hexahydroazepine, —(CH 2 ) n NH 2 ,—(CH 2 ) n NH(C 1 -C 6 alkyl), —(CH 2 ) n N(C 1 -C 6 alkyl) 2 , -1-oxo(C 1 -C 6 )alkyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, N—(C 1 -C 6 )alkylcarbamoyl, and each C 1 -C 1 alkyl group of 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —CH═CH—(C 1 -C 6 )alkyl, -1-oxo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyloxycarbonyl, or —N—(C 1 -C 6 )alkylcarbamoyl is substituted with —OH, —NH 2 , or —NAB, where A and B are as defined above.
50 . A compound according to claim 22 wherein X is -D-E-F and F is
and R 5 is 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n -piperazinyl, —(CH 2 ) n -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —CH═CH—(C 1 -C 6 )alkyl, —(CH 2 ) n —N-hexahydroazepine, —(CH 2 ) n NH 2 ,—(CH 2 ) n NH(C 1 -C 6 alkyl), —(CH 2 ) n N(C 1 -C 6 alkyl) 2 , -1-oxo(C 1 -C 6 )alkyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, N—(C 1 -C 6 )alkylcarbamoyl, and each C 1 -C 1 alkyl group of 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —CH═CH—(C 1 -C 6 )alkyl, -1-oxo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyloxycarbonyl, or —N—(C 1 -C 6 )alkylcarbamoyl is substituted with —OH, —NH 2 , or —NAB, where A and B are as defined above; or
Y is -D-E-F and F is
and R 5 is 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —(CH 2 ) n —N-piperidinyl. —(CH 2 ) n -piperazinyl, —(CH 2 ) n -piperazinyl[N 4 —(C 1 -C 6 )alkyl]. —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —CH═CH—(C 1 -C 6 )alkyl, —(CH 2 ) n —N-hexahydroazepine, —(CH 2 ) n NH 2 ,—(CH 2 ) n NH(C 1 -C 6 alkyl), —(CH 2 ) n N(C 1 -C 6 alkyl) 2 , -1-oxo(C 1 -C 6 )alkyl, carboxy, (C 1 -C 6 )alkyloxycarbonyl, N—(C 1 -C 6 )alkylcarbamoyl, and each C 1 -C 1 alkyl group of 1,1-difluoro(C 1 -C 6 )alkyl, C 1 -C 6 alkyl, —CH═CH—(C 1 -C 6 )alkyl, -1-oxo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyloxycarbonyl, or —N—(C 1 -C 6 )alkylcarbamoyl is substituted with —OH, —NH 2 , or —NAB, where A and B are as defined above.
51 . A compound according to claim 1 wherein X is -D-E-F;
Y is —SR 4 , —OR 4 , or —NHR 3 ;
and R 3 and R 4 are —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1— piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n -imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —(CH 2 ) n —N-hexahydroazepine or substituted C 1 -C 6 alkyl, wherein the substituents are selected from —OH, —NH 2 , or
A and B are independently hydrogen, C 1 -C 6 alkyl, —(CH 2 ) n OH, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1 -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n —N-pyridyl, —(CH 2 ) n -imidazoyl, or —(CH 2 ) n —N-imidazoyl; or
Y is -D-E-F;
X is —SR 4 , —OR 4 , or —NHR 3 ;
and R 3 and R 4 are —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1 piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl —(CH 2 ) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n -imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —(CH 2 ) n —N-hexahydroazepine or substituted C 1 -C 6 alkyl, wherein the substituents are selected from —OH, —NH 2 , or
A and B are independently hydrogen, C 1 -C 6 alkyl, —(CH 2 ) n OH, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, -(CH 2 ) n —N 1 -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n —N-pyridyl, —(CH 2 ) n -imidazoyl, or —(CH 2 ) n —N-imidazoyl.
52 . A compound according to claim 13 wherein X is -D-E-F;
Y is —SR 4 , —OR 4 , or —NHR 3 ;
and R 3 and R 4 are —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1— piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n -imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —(CH 2 ) n —N-hexahydroazepine or substituted C 1 -C 6 alkyl, wherein the substituents are selected from —OH, —NH 2 , or
A and B are independently hydrogen, C 1 -C 6 alkyl, —(CH 2 ) n OH, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1 -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n —N-pyridyl, —(CH 2 ) n -imidazoyl, or —(CH 2 ) n —N-imidazoyl; or
Y is -D-E-F;
X is —SR 4 , —OR 4 , or —NHR 3 ;
and R 3 and R 4 are —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1— piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n -imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —(CH 2 ) n —N-hexahydroazepine or substituted C 1 -C 6 alkyl, wherein the substituents are selected from —OH, —NH 2 , or
A and B are independently hydrogen, C 1 -C 6 alkyl, —(CH 2 ) n OH, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1 -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n —N-pyridyl, —(CH 2 ) n -imidazoyl, or —(CH 2 ) n —N-imidazoyl.
53 . A compound according to claim 22 wherein X is -D-E-F;
Y is —SR 4 , —OR 4 , or —NHR 3 ;
and R 3 and R 4 are —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1— piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n -imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —(CH 2 ) n —N-hexahydroazepine or substituted C 1 -C 6 alkyl, wherein the substituents are selected from —OH, —NH 2 , or
A and B are independently hydrogen, C 1 -C 6 alkyl, —(CH 2 ) n OH, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1 -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n —N-pyridyl, —(CH 2 ) n -imidazoyl, or —(CH 2 ) n —N-imidazoyl; or
Y is -D-E-F;
X is —SR 4 , —OR 4 , or —NHR 3 ;
and R 3 and R 4 are —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1— piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n -pyridinyl, —(CH 2 ) n —N-imidazoyl, —(CH 2 ) n -imidazoyl, —(CH 2 ) n —N-morpholino, —(CH 2 ) n —N-thiomorpholino, —(CH 2 ) n —N-hexahydroazepine or substituted C 1 -C 6 alkyl, wherein the substituents are selected from —OH, —NH 2 , or
A and B are independently hydrogen, C 1 -C 6 alkyl, —(CH 2 ) n OH, —(CH 2 ) n —N-piperidinyl, —(CH 2 ) n —N-piperazinyl, —(CH 2 ) n —N 1 -piperazinyl[N 4 —(C 1 -C 6 )alkyl], —(CH 2 ) n —N-pyrrolidyl, —(CH 2 ) n —N-pyridyl, —(CH 2 ) n -imidazoyl, or —(CH 2 ) n —N-imidazoyl.
54 . The compounds:
N-[4-(6-Bromo-2,3-dihydroindol-1-yl)quinazolin-6-yl]acrylamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]acrylamide; N-[4-(7-Chloro-3,4-dihydro-2H-quinolin-1-yl)quinazolin-6-yl]acrylamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-7-yl]acrylamide; N-[4-(7-Chloro-3,4-dihydro-2H-quinolin-1-yl)quinazolin-7-yl]acrylamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]propynamide; N-[4-(7-Trifluoromethyl-3,4-dihydro-2H-quinolin-1-yl)quinazolin-6-yl]propynamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-7-yl]propynamide; N-[4-(7-Trifluoromethyl-3,4-dihydro-2H-quinolin-1-yl)quinazolin-7-yl]propynamide; N-[4-(4-6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]but-2-ynamide; N-[4-(6-Bromo-5-fluoro-2,3-dihydroindol-1-yl)quinazolin-6-yl]but-2-ynamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]buta-2,3-dienamide; N-[4-(6-Bromo-5-fluoro-2,3-dihydroindol-1-yl)quinazolin-6-yl]buta-2,3-dienamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]but-2-enamide; N-[4-(6-Ethynyl-2,3-dihydroindol-1-yl)quinazolin-6-yl]but-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4,4,4-trifluorobut-2-enamide; N-[4-(6-Nitro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4,4,4-trifluorobut-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-3-chloroacryl-amide; N-[4-(6-Nitro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-3-chloroacrylamide; 6-(S-Vinylsulfonamido)-4-(6-chloro-2,3-dihydroindol-1-yl)quinazoline; 6-(S-Vinylsulfonamido)-4-(6-pyrrol-1-yl-2,3-dihydroindol-1-yl)quinazoline; N-[7-[3-(4-Morpholino)propoxy]-4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]acrylamide; N-[4-(6-Pyrrol-1-yl-2,3-dihydroindol-1-yl)-7-[4-(N,N-dimethylamino)butoxy]quinazolin-6-yl]acrylamide N-[7-[4-(N,N-dimethylamino)butoxy]-4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]acrylamide; N-[4-(Octahydroindol-1-yl)-7-[3-(4-morpholino)propoxy]-quinazolin-6-yl]acrylamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-oxopent-2-enamide; N-[4-(Octahydroindol-1-yl)quinazolin-6-yl]-4-oxopent-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-hydroxy-4-oxobut-2-enamide; N-[4-(6,7-Dihydro-5H-[1,3]dioxolo[4,5-f]indol-5-yl)quinazolin-6-yl]-4-hydroxy-4-oxobut-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-ethoxy-4-oxobut-2-enamide; N-[4-(6,7-Dihydro-5H-[1,3]dioxolo[4,5-f]indol-5-yl)quinazolin-6-yl]-4-ethoxy-4-oxobut-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-(3-(N,N-dimethylamino)propoxy)-4-oxobut-2-enamide; N-[4-(6-Methyl-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-(3-(N,N-dimethylamino)propoxy)-4-oxobut-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-(3-(N,N-dimethylamino)propylamino)-4-oxobut-2-enamide; N-[4-(6-Methyl-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-(3-(N,N-dimethylamino)propylamino)-4-oxobut-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-(3-(4-morpholino)propoxy)-4-oxobut-2-enamide; N-[4-(6-Azido-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-(3-(4-morpholino)propoxy)-4-oxobut-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-(3-(4-morpholino)propylamino)-4-oxobut-2-enamide; N-[4-(6-Azido-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-(3-(4-morpholino)propylamino)-4-oxobut-2-enamide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]amide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(5-benzyloxy-2,3-dihydroindol-1-yl)quinazolin-6-yl]amide; Pent-2-enedioic acid 1{[4-(5-benzyloxy-2,3-dihydroindol-1-yl)quinazolin-6-yl]amide}5-[(3-morpholin-4-ylpropyl)amide]; Pent-2-enedioic acid 1{[4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]amide}5-[(3-morpholin-4-ylpropyl)amide]; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enamide; N-[4-(5-Methoxy-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enamide; 7-Morpholin-4-ylhept-2-ynoic acid[4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]amide; 7-Morpholin-4-ylhept-2-ynoic acid[4-(5-methoxy-2,3-dihydroindol-1-yl)quinazolin-6-yl]amide; 4-Morpholin-4-ylbut-2-ynoic acid[4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]amide; 4-Morpholin-4-ylbut-2-ynoic acid[4-(2,3,4,5-tetrahydro-1H-benzoazepin-1-yl)quinazolin-6-yl]amide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]acrylamide; N-[4-(2,3,4,5-Tetrahydro-1H-benzoazepin-1-yl)pyrido[3,4-d]-pyrimid-6-yl]acrylamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[4,3-d]pyrimid-7-yl]acrylamide; N-[4-(5-Hydroxy-2,3-dihydroindol-1-yl)pyrido[4,3-d]pyrimid-7-yl]propynamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]propynamide; N-[4-(5-Hydroxy-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]propynamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[4,3-d]pyrimid-7-yl]propynamide; N-[4-(5-Amino-2,3-dihydroindol-1-yl)pyrido[4,3-d]pyrimid-7-yl]propynamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido [3,4-d]pyrimid-6-yl]but-2-ynamide; N-[4-(5-Amino-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]but-2-ynamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido [3,4-d]pyrimid-6-yl]buta-2,3-dienamide; N-[4-(1,2,3,4,5,6-Hexahydrobenzo[b]azocin-1-yl)pyrido[3,4-d]-pyrimid-6-yl]buta-2,3-dienamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]but-2-enamide; N-[4-(1,2,3,4,5,6-Hexahydrobenzo[b]azocin-1-yl)pyrido[3,4-d]-pyrimid-6-yl]but-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4,4,4-trifluorobut-2-enamide; N-[4-(6-Fluoro-7-methyl-2,3-dihydroindol-1-yl)pyrido[3,4-d]-pyrimid-6-yl]-4,4,4-trifluorobut-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-3-chloroacrylamide; N-[4-(6-Fluoro-7-methyl-2,3-dihydroindol-1-yl)pyrido[3,4-d]-pyrimid-6-yl]-3-chloroacrylamide; 6-(S-Vinylsulfonamido)-4-(6-chloro-2,3-dihydroindol-1-yl)-pyrido[3,4-d]pyrimidine; 6-(S-Vinylsulfonamido)-4-(2,3,6,7,8,9-hexahydro-1H-benzo[g]indol-1-yl)pyrido[3,4-d]pyrimidine. N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-oxopent-2-enamide; N-[4-(2,3,6,7,8,9-Hexahydro-1H-benzo[g]indol-1-yl)pyrido[3,4d]-pyrimid-6-yl]-4-oxopent-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-hydroxy-4-oxobut-2-enamide; N-[4-(6-Ethynyl-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-hydroxy-4-oxobut-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-ethoxy-4-oxobut-2-enamide; N-[4-(6-Ethynyl-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-ethoxy-4-oxobut-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(N,N-dimethylamino)propoxy)-4-oxobut-2-enamide; N-[4-(6-Ethynyl-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(N,N-dimethylamino)propoxy)-4-oxobut-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(N,N-dimethylamino)propylamino)-4-oxobut-2-enamide; N-[4-(6-Ethynyl-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(N,N-dimethylamino)propylamino)-4-oxobut-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(4-morpholino)propoxy)-4-oxobut-2-enamide; N-[4-(6-Ethynyl-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(4-morpholino)propoxy)-4-oxobut-2-enamide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(4-morpholino)propylamino)-4-oxobut-2-enamide; N-[4-(6-Ethynyl-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(4-morpholino)propylamino)-4-oxobut-2-enamide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(6-chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]amide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(6-Ethynyl-2.3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]amide; Pent-2-enedioic acid 1{[4-(2,3-dihydropyrrolo[2,3-f]indol-7-yl)pyrido[3,4-d]pyrimid-6-yl]amide}5-[(3-morpholin-4-ylpropyl)amide]; Pent-2-enedioic acid 1{[4-(6-chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]amide}5-[(3-morpholin-4-ylpropyl)amide]; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enamide; N-[4-(2,3-Dihydropyrrolo[2,3-f]indol-7-yl)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enamide; 7-Morpholin-4-ylhept-2-ynoic acid[4-(6-chloro-2,3-dihydroindol-1-yl)pyrido [3,4-d]pyrimid-6-yl]amide; 7-Morpholin-4-ylhept-2-ynoic acid[4-(2,3,5,6-tetrahydropyrrolo[2,3-f]indol-1-yl)pyrido[3,4-d]pyrimid-6-yl]amide; 4-Morpholin-4-ylbut-2-ynoic acid[4-(6-chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimid-6-yl]amide; 4-Morpholin-4-ylbut-2-ynoic acid[4-(2,3,5,6-tetrahydropyrrolo[2,3-f]indol-1-yl)pyrido[3,4-d]pyrimid-6-yl]amide; N-[4-(6-Chloro-2,3-dihydroindol-1-yl)benzo[b]thieno[3,2-d]-pyrimid-6-yl]acrylamide; N-[4-(6-Ethynyl-2,3-dihydroindol-1-yl)benzo[b]thieno[3,2-d]-pyrimid-6-yl]acrylamide; [4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]acrylate; [4-(2,3,5,6-Tetrahydropyrrolo[2,3-f]indol-1-yl)quinazolin-6-yl]acrylate; [4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-7-yl]acrylate; [4-(6-Ethynyl-2,3-dihydroindol-1-yl)quinazolin-7-yl]acrylate; [7-[3-(4-Morpholino)propoxy]-4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]acrylate; [4-(-(2,3-Dihydropyrrolo[2,3-f]indol-7-yl)-7-[4-(N,N-dimethylamino)butoxy]quinazolin-6-yl]acrylate; [7-[4-(N,N-dimethylamino)butoxy]-4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]acrylate; [4-(6-Ethynyl-2,3-dihydroindol-1-yl)-7-[3-(4-morpholino)-propoxy]quinazolin-6-yl]acrylate; N-(3-(4-Morpholino)propylamino)-4,O-[4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-oxobut-2-enamide; N-(3-(4-Morpholino)propylamino)-4,O-[4-(2,3,4,5-tetrahydro-1H-benzoazepin-1-yl)quinazolin-6-yl]-4-oxobut-2-enamide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]ester; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(6-bromo-2,3-dihydroindol-1-yl)quinazolin-6-yl]ester; Pent-2-enedioic acid 1{[4-(6-methyl-2,3-dihydroindol-1-yl)quinazolin-6-yl]ester}5-[(3-morpholin-4-ylpropyl)amide]; Pent-2-enedioic acid 1{[4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]ester}5-[(3-morpholin-4-ylpropyl)amide]; [4-(6-Chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enoate; [4-(6-Fluoro-2,3-dihydroindol-1-yl)quinazolin-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enoate; 7-Morpholin-4-ylhept-2-ynoic acid[4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]ester; 7-Morpholin-4-ylhept-2-ynoic acid[4-(6-chloro-7-fluoro-2,3-dihydroindol-1-yl)quinazolin-6-yl]ester; 4-Morpholin-4-ylbut-2-ynoic acid[4-(6-chloro-2,3-dihydroindol-1-yl)quinazolin-6-yl]ester; 4-Morpholin-4-ylbut-2-ynoic acid[4-(6-ethynyl-2,3-dihydroindol-1-yl)quinazolin-6-yl]ester; N-[4-(Quinol-2-ylamino)quinazolin-6-yl]acrylamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]acrylamide; N-[4-(Quinol-2-ylamino)quinazolin-7-yl]acrylamide; N-[4-(Indol-5-ylamino)quinazolin-7-yl]acrylamide; N-[4-(Quinol-3-ylamino)quinazolin-6-yl]propynamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]propynamide; N-[4-(Quinol-3-ylamino)quinazolin-7-yl]propynamide; N-[4-(Indol-5-ylamino)quinazolin-7-yl]propynamide; N-[4-(Quinol-5-ylamino)quinazolin-6-yl]but-2-ynamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]but-2-ynamide; N-[4-(Quinol-5-ylamino)quinazolin-6-yl]buta-2,3-dienamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]buta-2,3-dienamide; N-[4-(Quinol-6-ylamino)quinazolin-6-yl]but-2-enamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]but-2-enamide; N-[4-(Quinol-6-ylamino)quinazolin-6-yl]4,4,4-trifluorobut-2-enamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]-4,4,4-trifluorobut-2-enamide; N-[4-(Quinol-7-ylamino)quinazolin-6-yl]-3-chloroacrylamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]-3-chloroacrylamide; 6-(S-Vinylsulfonamido)-4-(quinol-7-ylamino)quinazoline; 6-(S-Vinylsulfonamido)-4-(indol-5-ylamino)quinazoline; N-[7-[3-(4-Morpholino)propoxy]-4-(quinol-8-ylamino)quinazolin-6-yl]acrylamide; N-[4-(Indol-5-ylamino)-7-[4-(N,N-dimethylamino)butoxy]-quinazolin-6-yl]acrylamide; N-[7-[4-(N,N-dimethylamino)butoxy]-4-(quinol-8-ylamino)-quinazolin-6-yl]acrylamide; N-[4-(Indol-5-ylamino)-7-[3-(4-morpholino)propoxy]quinazolin-6-yl]acrylamide; N-[4-(Isoquinol-1-ylamino)quinazolin-6-yl]-4-oxopent-2-enamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]-4-oxopent-2-enamide; N-[4-(Isoquinol-1-ylamino)quinazolin-6-yl]-4-hydroxy-4-oxobut-2-enamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]-4-hydroxy-4-oxobut-2-enamide; N-[4-(Isoquinol-5-ylamino)quinazolin-6-yl]-4-ethoxy-4-oxobut-2-enamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]-4-ethoxy-4-oxobut-2-enamide; N-[4-(Isoquinol-5-ylamino)quinazolin-6-yl]-4-(3-(N,N-dimethylamino)propoxy)-4-oxobut-2-enamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]-4-(3-(N,N-dimethylamino)-propoxy)-4-oxobut-2-enamide; N-[4-(Indol-4-ylamino)quinazolin-6-yl]-4-(3-(N,N-dimethylamino)propylamino)-4-oxobut-2-enamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]-4-(3-(N,N-dimethylamino)propylamino)-4-oxobut-2-enamide; N-[4-(Indol-4-ylamino)quinazolin-6-yl]-4-(3-(4-morpholino)propoxy)-4-oxobut-2-enamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]-4-(3-(4-morpholino)propoxy)-4-oxobut-2-enamide; N-[4-(Indol-6-ylamino)quinazolin-6-yl]-4-(3-(4-morpholino)propylamino)-4-oxobut-2-enamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]-4-(3-(4-morpholino)propylamino)-4-oxobut-2-enamide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(indol-6-ylamino)quinazolin-6-yl]amide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(indol-5-ylamino)quinazolin-6-yl]amide; Pent-2-enedioic acid 1{[4-(indol-5-ylamino)quinazolin-6-yl]amide}5-[(3-morpholin-4-ylpropyl)amide]; Pent-2-enedioic acid 1{[4-(1H-indazol-6-ylamino)quinazolin-6-yl]amide}5-[(3-morpholin-4-ylpropyl)amide]; N-[4-(1H-Indazol-6-ylamino)quinazolin-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enamide; N-[4-(Indol-5-ylamino)quinazolin-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enamide; 7-Morpholin-4-ylhept-2-ynoic acid[4-(1H-indazol-5-ylamino)quinazolin-6-yl]amide; 7-Morpholin-4-ylhept-2-ynoic acid[4-(indol-5-ylamino)quinazolin-6-yl]amide; 4-Morpholin-4-ylbut-2-ynoic acid[4-(1H-indazol-5-ylamino)quinazolin-6-yl]amide; 4-Morpholin-4-ylbut-2-ynoic acid[4-(4-benzyloxyphenylamino)-quinazolin-6-yl]amide; N-[4-(1H-Indazol-4-ylamino)pyrido[3,4-d]pyrimid-6-yl]acrylamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]acrylamide; N-[4-(1H-Indazol-4-ylamino)pyrido[4,3-d]pyrimid-7-yl]acrylamide; N-[4-(Indol-5-ylamino)pyrido[4,3-d]pyrimid-7-yl]propynamide; N-[4-(1H-Indazol-4-ylamino)pyrido[3,4-d]pyrimid-6-yl]propynamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]propynamide; N-[4-(1H-Benzotriazol-5-ylamino)pyrido[4,3-d]pyrimid-7-yl]propynamide; N-[4-(Indol-5-ylamino)pyrido[4,3- d]pyrimid-7-yl]propynamide; N-[4-(1H-Benzotriazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]but-2-ynamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]but-2-ynamide; N-[4-(1H-Benzotriazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]buta-2,3-dienamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]buta-2,3-dienamide; N-[4-(1H-Benzotriazol-7-ylamino)pyrido[3,4-d]pyrimid-6-yl]but-2-enamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid -6-yl]but-2-enamide; N-[4-(1H-Benzotriazol-7-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4,4,4-trifluorobut-2-enamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4,4,4-trifluorobut-2-enamide; N-[4-(1H-Benzotriazol-7-ylamino)pyrido[3,4-d]pyrimid-6-yl]-3-chloroacrylamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-3-chloroacrylamide; 6-(S-Vinylsulfonamido)-4-(benzothiazol-5-ylamino)pyrido[3,4-d]-pyrimidine; 6-(S-Vinylsulfonamido)-4-(indol-5-ylamino)pyrido [3,4-d]-pyrimidine; N-[4-(Benzothiazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-oxopent-2-enamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-oxopent-2-enamide; N-[4-(Benzothiazol-6-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-hydroxy-4-oxobut-2-enamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-hydroxy-4-oxobut-2-enamide; N-[4-(Benzothiazol-6-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-ethoxy-4-oxobut-2-enamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-ethoxy-4-oxobut-2-enamide; N-[4-(Indan-4-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(N,N-dimethylamino)propoxy)-4-oxobut-2-enamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(N,N-dimethylamino)propoxy)-4-oxobut-2-enamide; N-[4-(Indan-4-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(N,N-dimethylamino)propylamino)-4-oxobut-2-enamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(N,N-dimethylamino)propylamino)-4-oxobut-2-enamide; N-[4-(Indan-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(4-morpholino)propoxy)-4-oxobut-2-enamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(4-morpholino)propoxy)-4-oxobut-2-enamide; N-[4-(Indan-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(4-morpholino)propylamino)-4-oxobut-2-enamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(4-morpholino)propylamino)-4-oxobut-2-enamide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(1,2,3,4-tetrahydronaphth-1-ylamino)pyrido[3,4-d]pyrimid-6-yl]amide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]amide; Pent-2-enedioic acid 1{[4-(indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]amide}5-[(3-morpholin-4-ylpropyl)amide]; Pent-2-enedioic acid 1{[4-(1,2,3,4-tetrahydronaphth-1-ylamino)pyrido[3,4-d]pyrimid-6-yl]amide}5-[(3-morpholin-4-ylpropyl)amide]; N-[4-(1,2,3,4-Tetrahydronaphth-2-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enamide; N-[4-(Indol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enamide; 7-Morpholin-4-ylhept-2-ynoic acid[4-(1,2,3,4-tetrahydronaphth-2-ylamino)pyrido[3,4-d]pyrimid-6-yl]amide; 7-Morpholin-4-ylhept-2-ynoic acid[4-(indol-5-ylamino)-pyrido[3,4-d]pyrimid-6-yl]amide; 4-Morpholin-4-ylbut-2-ynoic acid[4-(benzo[c][2,1,3]thiadiazol-4-ylamino)pyrido[3,4-d]pyrimid-6-yl]amide: 4-Morpholin-4-ylbut-2-ynoic acid[4-(indol-5-ylamino)-pyrido[3,4-d]pyrimid-6-yl]amide; N-[4-(Benzo[c][2,1,3]thiadiazol-4-ylamino)benzo[b]thieno[3,2-d]-pyrimid-6-yl]acrylamide; N-[4-(Indol-5-ylamino)benzo[b]thieno[3,2-d]pyrimid-6-yl]acrylamide; [4-(Benzimidazol-5-ylamino)quinazolin-6-yl]acrylate; [4-(Indol-5-ylamino)quinazolin-6-yl]acrylate. [4-(Benzimidazol-5-ylamino)quinazolin-7-yl]acrylate; [4-(Indol-5-ylamino)quinazolin-7-yl]acrylate; [7-[3-(4-Morpholino)propoxy]-4-(benzimidazol-5-ylamino)-5quinazolin-6-yl]acrylate; [4-(Indol-5-ylamino)-7-[4-(N,N-dimethylamino)butoxy]-quinazolin-6-yl]acrylate; [7-[4-(N,N-dimethylamino)butoxy]-4-(6-methoxyquinol-8-ylamino)quinazolin-6-yl]acrylate; [4-(Indol-5-ylamino)-7-[3-(4-morpholino)propoxy]quinazolin-6-yl]acrylate; N-(3-(4-Morpholino)propylamino)-4,O-[4-(6-methoxyquinol-8-ylamino)quinazolin-6-yl]-4-oxobut-2-enamide; N-(3-(4-Morpholino)propylamino)-4,O-[4-(indol-5-ylamino)-quinazolin-6-yl]-4-oxobut-2-enamide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(1-methylindol-5-ylamino)quinazolin-6-yl]ester; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(indol-5-ylamino)quinazolin-6-yl]ester; Pent-2-enedioic acid 1{[4-(indol-5-ylamino)quinazolin-6-yl]ester}5-[(3-morpholin-4-ylpropyl)amide]; Pent-2-enedioic acid 1{[4-(1-methylindol-5-ylamino)quinazolin-6-yl]ester}5-[(3-morpholin-4-ylpropyl)amide]; [4-(2-Methylindol-5-ylamino)quinazolin-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enoate; [4-(Indol-5-ylamino)quinazolin-6-yl]-4-(3-(morpholin-4-yl)-propylthio)but-2-enoate; 7-Morpholin-4-ylhept-2-ynoic acid[4-(3-cyanoindol-5-ylamino)-quinazolin-6-yl]ester; 7-Morpholin-4-ylhept-2-ynoic acid[4-(indol-5-ylamino)-quinazolin-6-yl]ester; 4-Morpholin-4-ylbut-2-ynoic acid[4-(benzothien-5-ylamino)-quinazolin-6-yl]ester; 4-Morpholin-4-ylbut-2-ynoic acid[4-(indol-5-ylamino)quinazolin-6-yl]ester; N-[4-(1-Benzylindol-5-ylamino)quinazolin-6-yl]acrylamide; N-[4-(2-Benzylbenzimidazol-5-ylamino)quinazolin-6-yl]acrylamide; N-[4-( l -Benzylindol-5-ylamino)quinazolin-7-yl]acrylamide; N-[4-(2-Benzylbenzimidazol-5-ylamino)quinazolin-7-yl]acrylamide; N-[4-(2-Benzylbenzindazol-5-ylamino)quinazolin-6-yl]propynamide; N-[4-(1-Benzylbenzindazol-5-ylamino)quinazolin-6-yl]propynamide; N-[4-(2-Benzylbenzindazol-5-ylamino)quinazolin-7-yl]propynamide; N-[4-(2-Benzylbenzindazol-5-ylamino)quinazolin-7-yl]propynamide; N-[4-(1-Phenylsulfonylindol-5-ylamino)quinazolin-6-yl]but-2-ynamide; N-[4-(1-Phenylsulfonylindol-5-ylamino)quinazolin-6-yl]buta-2,3-dienamide; N-[4-(1-Benzylindol-5-ylamino)quinazolin-6-yl]but-2-enamide; N-[4-(2-Benzylbenzindazol-5-ylamino)quinazolin-6-yl]-4,4,4-trifluorobut-2-enamide; N-[4-(1-Benzylindol-5-ylamino)quinazolin-6-yl]-4,4,4-trifluorobut-2-enamide; N-[4-(1-Benzylindol-6-ylamino)quinazolin-6-yl]-3-chloroacrylamide; 6-(S-Vinylsulfonamido)-4-(2-benzylbenzindazol-5-ylamino)quinazoline; N-[7-[3-(4-Morpholino)propoxy]-4-(2-benzylbenzindazol-5-ylamino)quinazolin-6-yl]acrylamide; N-[4-(1-Benzylindol-6-ylamino)-7-[4-(N,N-dimethylamino)-butoxy]quinazolin-6-yl]acrylamide; N-[4-(2-Phenylbenzimidazol-5-ylamino)-7-[3-(4-morpholino)-propoxy]quinazolin-6-yl]acrylamide; N-[4-(2-Phenylbenzimidazol-5-ylamino)quinazolin-6-yl]-4-oxopent-2-enamide; N-[4-(3-Benzylbenzimidazol-5-ylamino)quinazolin-6-yl]-4-hydroxy-4-oxobut-2-enamide; N-[4-(3-Benzylbenzimidazol-5-ylamino)quinazolin-6-yl]-4-ethoxy-4-oxobut-2-enamide; N-[4-(2-Benzylbenzindazol-5-ylamino)quinazolin-6-yl]-4-(3-(N,N-dimethylamino)propoxy)-4-oxobut-2-enamide; N-[4-(2-Benzylbenzindazol-5-ylamino)quinazolin-6-yl]-4-(3-(N,N-dimethylamino)propylamino)-4-oxobut-2-enamide; N-[4-(1-Benzylbenzimidazol-5-ylamino)quinazolin-6-yl]-4-(3-(N,N-dimethylamino)propylamino)-4-oxobut-2-enamide; N-[4-(1-Benzylbenzimidazol-5-ylamino)quinazolin-6-yl]-4-(3-(4-morpholino)propoxy)-4-oxobut-2-enamide; N-[4-(2-Benzylbenzindazol-5-ylamino)quinazolin-6-yl]-4-(3-(4-morpholino)propoxy)-4-oxobut-2-enamide; N-[4-(42-Benzylbenzindazol-5-ylamino)quinazolin-6-yl]-4-(3-(4-morpholino)propylamino)-4-oxobut-2-enamide; N-[4-(2-Benzylbenzotriazol-5-ylamino)quinazolin-6-yl]-4-(3-(4-morpholino)propylamino)-4-oxobut-2-enamide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(2-benzylbenzotriazol-5-ylamino)quinazolin-6-yl]amide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(2-benzylbenzindazol-5-ylamino)quinazolin-6-yl]amide; Pent-2-enedioic acid 1{[4-(2-benzylbenzindazol-5-ylamino)quinazolin-6-yl]amide }5-[(3-morpholin-4-ylpropyl)amide]; Pent-2-enedioic acid 1{[4-(2-benzylbenzindazol-5-ylamino)quinazolin-6-yl]amide}5-[(3-morpholin-4-ylpropyl)amide]; N-[4-(1-Benzylbenzotriazol-5-ylamino)quinazolin-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enamide; N-[4-(2-Benzylbenzindazol-5-ylamino)quinazolin-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enamide; 7-Morpholin-4-ylhept-2-ynoic acid[4-(1-Benzylbenzotriazol-5-ylamino)quinazolin-6-yl]amide; 4-Morpholin-4-ylbut-2-ynoic acid[4-(3-benzylbenzotriazol-5-ylamino)quinazolin-6-yl]amide; 4-Morpholin-4-ylbut-2-ynoic acid[4-(2-benzylbenzindazol-5-ylamino)quinazolin-6-yl]amide; N-[4-(2-Benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]acrylamide; N-[4-(3-Benzylbenzotriazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]acrylamide; N-[4-(2-{Pyrid-2-yl}benzotriazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]propynamide; N-[4-(2-Benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]propynamide; N-[4-(2-{Pyrid-2-yl}benzotriazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]but-2-ynamide; N-[4-(2-Benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]buta-2,3-dienamide; N-[4-(2-Phenethylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]but-2-enamide; N-[4-(2-Phenethylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4,4,4-trifluorobut-2-enamide; N-[4-(2-Benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4,4,4-trifluorobut-2-enamide; N-[4-(1-Phenethylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-3-chloroacrylamide; 6-( S-Vinylsulfonamido)-4-(1-phenethylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimidine; 6-(S-Vinylsulfonamido)-4-(2-benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimidine; N-[4-(2-Benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-hydroxy-4-oxobut-2-enamide; N-[4-(2-Benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(N,N-dimethylamino)propylamino)-4-oxobut-2-enamide; N-[4-(2-Benzyloxyindol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(4-morpholino)propoxy)-4-oxobut-2-enamide; N-[4-(2-Benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(4-morpholino)propoxy)-4-oxobut-2-enamide; N-[4-(2-Benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(4-morpholino)propylamino)-4-oxobut-2-enamide; N-[4-(2-Benzyloxyindol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(4-morpholino)propylamino)-4-oxobut-2-enamide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(2-benzyloxybenzimidazol-5-ylamino)pyrido[3 4-d]pyrimid-6-yl]amide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(2-benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]amide; Pent-2-enedioic acid 1{[4-(2-benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]amide}5-[(3-morpholin-4-ylpropyl)amide]; Pent-2-enedioic acid 1{[4-(2-benzylsulfonylbenzimidazol-5-ylamino) pyrido[3,4-d]pyrimid-6-yl]amide}5-[(3-morpholin-4-ylpropyl)amide]; N-[4-(4-benzyloxybenzimidazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enamide; N-[4-(2-Benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enamide; 7-Morpholin-4-ylhept-2-ynoic acid[4-(2-benzylbenzindazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]amide; 7-Morpholin-4-ylhept-2-ynoic acid[4-(2-benzylsulfonylbenzimidazol-5-ylamino)pyrido[3,4-d]pyrimid-6-yl]amide: N-[4-(2-Benzylbenzindazol-5-ylamino)benzo[b]thieno [3,2-d]-pyrimid-6-yl]acrylamide; N-[4-(1-Benzylbenzindazol-5-ylamino)benzo[b]thieno[3,2-d]-pyrimid-6-yl]acrylamide; [4-(2-Benzylbenzindazol-5-ylamino)quinazolin-6-yl]acrylate; N-(3-(4-Morpholino)propylamino)-4,O-[4-(2-benzylbenzindazol-5-ylamino)quinazolin-6-yl]-4-oxobut-2-enamide; 4,4-Difluoro-8-(morpholin-4-yl)oct-2-enoic acid[4-(2-benzylbenzindazol-5-ylamino)quinazolin-6-yl]ester; Pent-2-enedioic acid 1{[4-(2-benzylbenzindazol-5-ylamino)quinazolin-6-yl]ester}5-[(3-morpholin-4-ylpropyl)amide]; [4-(2-Benzylbenzindazol-5-ylamino)quinazolin-6-yl]-4-(3-(morpholin-4-yl)propylthio)but-2-enoate; and 7-Morpholin-4-ylhept-2-ynoic acid[4-(2-benzylbenzindazol-5-ylamino)quinazolin-6-yl]ester.Join the waitlist — get patent alerts
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