Kinase inhibitors
View Patent ↗A compound having the general structure of Formula (I): or a pharmaceutically acceptable salt, solvate, or ester thereof, are useful in treating diseases, disorders, or conditions such as immunodeficiencies, cancers, cardiovascular diseases, endocrine disorders, Parkinson's disease, metabolic diseases, tumorigenesis, Alzheimer's disease, heart disease, diabetes, neurodegeneration, inflammation, kidney disease, atherosclerosis and airway disease.
1. A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
A 1 is selected from the group consisting of a covalent bond, and
A 2 is selected from the group consisting of a covalent bond, alkylene, alkenylene, alkynylene, cycloalkylene, —O—, —N(R 5 )—, —C(O)—, —S—, —S(O)—, —S(O) 2 —, —S(O) 2 —N(R 6 )—, —N(R 6 )—S(O) 2 —, —C(R 7 ) 2 —N(R 5 )—, —N(R 5 )—C(R 7 ) 2 —, —C(O)—N(R 6 )—, —N(R 6 )—C(O)—, —N(R 6 )—C(O)—N(R 6 )—, —C(R 7 ) 2 —C═N—, and —N═C—C(R 7 ) 2 —;
A 3 is selected from the group consisting of a covalent bond, cyclopropylene, alkenylene, alkynylene, —N(R 5 )—, —O—, —S—, —S(O) 2 —, —C(O)N(R 6 )—, and —N(R 6 )C(O)—;
R 1 and R 2 are each independently selected from the group consisting of H, alkyl, haloalkyl, one or more hydroxyl substituted alkyl, alkenyl, alkynyl, alkoxy, -alkylene-O-alkyl, aryl, -alkylene-aryl, —CN, halogen, heteroaryl, -alkylene-heteroaryl, cycloalkyl, heterocyclyl, and -alkylene-heterocyclyl,
wherein said aryl, heteroaryl, the aryl portion of said -alkylene-aryl, or the heteroaryl portion of said -alkylene-heteroaryl of R 1 or R 2 are unsubstituted or substituted with one or more groups Y which are independently selected; said heterocyclyl or the heterocyclyl portion of said -alkylene-heterocyclyl of R 1 or R 2 are unsubstituted or substituted with one or more groups Z which are independently selected; and
with the proviso that:
1) if R 1 and/or R 2 are alkoxy, the oxygen atom of said alkoxy is not bonded to a S, N, or O atom of A 1 or A 2 ,
2) if R 1 and/or R 2 are —CN, said —CN is not bonded to a S, N, or O atom of A 1 or A 2 ,
3) if R 1 is halogen, A 1 is a covalent bond, and
4) if R 2 is halogen, A 2 is a covalent bond;
R 3 is selected from the group consisting of H, alkyl, haloalkyl, cycloalkyl, alkoxy, —N(R 8 ) 2 , —N(R 8 )—C(O)—R 8 , —C(O)—N(R 6 ) 2 , —N(R 6 )—C(O)—N(R 6 ) 2 , —N(R 6 )—S(O) 2 —R 6 , —C(O)-alkyl, -alkylene-O-alkyl, —CN, halogen, aryl, heteroaryl, heterocyclyl, -alkylene-aryl, -alkylene-heteroaryl, alkylene-heterocyclyl, and alkynyl,
wherein said aryl, heteroaryl, the aryl portion of said -alkylene-aryl, or the heteroaryl portion of said -alkylene-heteroaryl of R 3 are unsubstituted or substituted with one or more groups Y which are independently selected; said heterocyclyl or the heterocyclyl portion of said alkylene-heterocyclyl of R 3 are unsubstituted or substituted with one or more groups Z which are independently selected;
R 4 is selected from the group consisting of H, alkyl, —C(O)-alkyl, —C(O)—O-alkyl, alkylene-O-alkyl, and -alkylene-O—C(O)-alkyl;
R 5 is selected from the group consisting of H, alkyl, cycloalkyl, haloalkyl, -alkylene-N(R 8 ) 2 , alkoxy, aryl, heteroaryl, -alkylene-aryl, -alkylene-heteroaryl, —C(O)-alkyl, —S(O) 2 -alkyl, —C(O)-aryl, —C(O)N(R 9 ) 2 , —C(O)-aryl, —C(O)-alkylene-aryl, —C(O)-heteroaryl, C(O)-alkylene-heteroaryl, —S(O) 2 -aryl, —S(O) 2 -alkylene-aryl, —S(O) 2 -heteroaryl, and —S(O) 2 -alkylene-heteroaryl,
wherein said aryl, the aryl portion of —C(O)-aryl, the aryl portion of -alkylene-aryl, or the aryl portion of —S(O) 2 -aryl of R 5 are unsubstituted or substituted with one or more groups Y which are independently selected;
each R 6 is independently selected from the group consisting of H, alkyl, cycloalkyl, haloalkyl, heterocyclyl, aryl, heteroaryl, -alkylene-heterocyclyl, -alkylene-aryl, and -alkylene-heteroaryl,
wherein said aryl or the aryl portion of alkylene-aryl of R 6 are unsubstituted or substituted with one or more groups Y which are independently selected;
each R 7 is independently selected from the group consisting of H, alkyl, cycloalkyl, haloalkyl, alkenyl, alkynyl, —N(R 8 ) 2 , —CN, halo, aryl, heteroaryl, heterocyclyl, -alkylene-heterocyclyl, -alkylene-aryl, and -alkylene-heteroaryl,
wherein said aryl, the aryl portion of said -alkylene-aryl, and said heteroaryl of R 7 are unsubstituted or substituted with one or more groups Y which are independently selected;
each R 8 is independently selected from the group consisting of H, alkyl, cycloalkyl, heterocyclyl, -alkylene-heterocyclyl, haloalkyl, -alkylene-aryl, aryl, heteroaryl, and -alkylene-heteroaryl,
wherein said aryl of R 8 is unsubstituted or substituted with one or more groups Y which are independently selected;
X is one or more substituents independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, —OR 9 , —N(R 5 ) 2 , and —C(O)N(R 6 ) 2 ;
Y is one or more substituents independently selected from the group consisting of halogen, alkyl, haloalkyl, aryl, -alkylene-aryl, —OH, —OR 9 , —CN, —NO 2 , —N(R 9 ) 2 , —N(R 9 )—C(O)—R 9 , —N(R 9 )—C(O)—N(R 9 ) 2 , —C(O)N(R 9 ) 2 , —C(O)OH, —C(O)O-alkyl, —N(R 9 )—S(O) 2 —(R 9 ) 2 and —S(O) 2 N(R 9 ) 2 ;
each R 9 is independently selected from the group consisting of H, alkyl, cycloalkyl, haloalkyl, heterocyclyl, -alkylene-heterocyclyl, aryl, -alkylene-aryl, heteroaryl, -alkylene-heteroaryl; and
Z is one or more substituents independently selected from the group consisting of alkyl, one or more hydroxy substituted alkyl, aryl, -alkylene-aryl, -alkylene-O-alkyl, -alkylene-O-alkylene-aryl, -alkylene-O-aryl, —CN, haloalkyl, -alkylene-C(O)—N(R 8 ) 2 , —C(O)—N(R 8 ) 2 , —C(O)OH, —C(O)O-alkyl, —N(R 8 ) 2 , and -alkylene-N(R 8 ) 2 , —S(O) 2 —N(R 8 ) 2 , -alkylene-S(O) 2 —N(R 8 ) 2 , —N(R 8 )—C(O)—R 8 , —N(R 8 )—C(O)—N(R 8 ) 2 , -alkylene-N(R 8 )—C(O)—N(R 8 ) 2 , -alkylene-N(R 8 )—C(O)—R 8 , -alkylene-S(O) 2 —R 8 , —N(R 8 )—S(O) 2 —R 8 , and -alkylene-N(R 8 )—S(O) 2 —R 8 , cycloalkyl, heterocyclyl, -alkylene-heterocyclyl, heteroaryl, and -alkylene-heteroaryl, or wherein two Z substitutents on adjacent carbon atoms, on a carbon atom and an adjacent heteroatom, or on a single carbon atom, together with the carbon atom(s) and/or the combination of the carbon atom and the adjacent heteroatom to which said Z substituents are attached form a four to seven-membered cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl ring;
wherein said aryl, heteroaryl, the aryl portion of said -alkylene-aryl, -alkylene-O-alkylene-aryl, -alkylene-O-aryl, and the heteroaryl portion of said -alkylene-heteroaryl are unsubstituted or substituted with one or more R 10 substitutents which are independently selected; and
R 10 is one or more substituents independently selected from the group consisting of halogen, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, nitro, —NH 2 , —NH(alkyl), —N(alkyl) 2 , hydroxyl, aryl, aryloxy, —O-alkylene-aryl, —NH(alkyl), —N(alkyl) 2 , —NH(aryl), —N(aryl) 2 , —NH-alkyene-aryl, —N(alkyl)-alkylene-aryl, -alkylene-aryl, —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl) 2 , —S(O) 2 NH 2 , —S(O) 2 NH(alkyl), —S(O) 2 N(alkyl) 2 , —NHC(O)-alkyl, —N(alkyl)C(O)-alkyl, —NHC(O)-aryl, —N(alkyl)C(O)-aryl, —NH—S(O) 2 -alkyl, —N(alkyl)-S(O) 2 -alkyl, —NH—S(O) 2 -aryl, and —N(alkyl)-S(O) 2 -aryl.
2. The compound of claim 1 , wherein A 2 is a covalent bond or —N(R 5 ).
3. The compound of claim 1 , wherein A 3 is a covalent bond.
4. The compound of claim 1 , wherein R 1 is H or (C 2 -C 6 )heterocyclyl.
5. The compound of claim 1 , wherein R 2 is H, —(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 4 )alkylene-(C 2 -C 10 )heteroaryl or halogen.
6. The compound of claim 1 , wherein R 3 is H, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, —(C 6 -C 10 )aryl, halogen, or —NH 2 .
7. The compound of claim 1 , wherein R 4 is H.
8. The compound of claim 1 , wherein R 5 is H or —(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl.
9. The compound of claim 1 , wherein X is H or (C 1 -C 6 )alkyl.
10. The compound of claim 1 , wherein Y is one or more substituents independently selected from the group consisting of halogen, alkyl, haloalkyl, aryl, —O-alkyl, —CN, and —NO 2 .
11. The compound of claim 1 , wherein Z is one or more substituents independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, —(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 4 )alkylene-(C 2 -C 10 )heteroaryl, —(C 1 -C 4 )alkylene-O—(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 6 )alkylene-OH, —N(R 8 ) 2 , —(C 1 -C 4 )alkylene-N(R 8 ) 2 , —C(O)O—(C 1 -C 6 )alkyl, and —C(O)OH, or wherein two Z substitutents on adjacent carbon atoms, on a carbon atom and an adjacent heteroatom, or on a single carbon atom, together with the carbon atom(s) and/or the combination of the carbon atom and the adjacent heteroatom to which said Z substituents are attached together form a four to seven-membered cycloalkyl or heterocyclyl ring,
wherein wherein said aryl, heteroaryl, the aryl portion of said -alkylene-aryl, -alkylene-O-alkylene-aryl, -alkylene-O-aryl, and the heteroaryl portion of said -alkylene-heteroaryl are unsubstituted or substituted with one or more R 10 substitutents which are independently selected; and
R 10 is one or more substituents independently selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, and hydroxyalkyl.
12. The compound of claim 1 , wherein:
A 2 is a covalent bond or —N(R 5 )—;
A 3 is a covalent bond;
R 1 is H or (C 2 -C 6 )heterocyclyl; wherein said (C 2 -C 6 )heterocyclyl of R 1 is unsubstituted or substituted with one of more groups Z;
R 2 is H, —(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 4 )alkylene-(C 2 -C 10 )heteroaryl or halogen; wherein said (C 6 -C 10 )aryl portion of —(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl of R 2 and said (C 2 -C 10 )heteroaryl portion of —(C 1 -C 4 )alkylene-(C 2 -C 10 )heteroaryl of R 2 are independently unsubstituted or substituted with one or more groups Y;
R 3 is H, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, —(C 6 -C 10 )aryl, halogen, or —NH 2 ;
R 4 is H;
R 5 is H or —(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl;
X is H or (C 1 -C 6 )alkyl;
Y is one or more substituents independently selected from the group consisting of halogen, alkyl, haloalkyl, aryl, —O-alkyl, —CN, and —NO 2 .
Z is one or more substituents independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, —(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 4 )alkylene-(C 2 -C 10 )heteroaryl, —(C 1 -C 4 )alkylene-O—(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 6 )alkylene-OH, —N(R 8 ) 2 , —(C 1 -C 4 )alkylene-N(R 8 ) 2 , —C(O)O—(C 1 -C 6 )alkyl, and —C(O)OH, or wherein two Z substitutents on adjacent carbon atoms, on a carbon atom and an adjacent heteroatom, or on a single carbon atom, together with the carbon atom(s) and/or the combination of the carbon atom and the adjacent heteroatom to which said Z substituents are attached together form a four to seven-membered cycloalkyl or heterocyclyl ring.
13. The compound of claim 1 , wherein:
A 1 is a covalent bond; and
R 1 is (C 2 -C 6 )heterocyclyl; wherein said (C 2 -C 6 )heterocyclyl of R 1 is unsubstituted or substituted with one of more groups Z.
14. The compound of claim 13 , wherein:
R 1 is selected from the group consisting of unsubstituted piperazinyl, unsubstituted piperidinyl, unsubstituted pyrrolidinyl, and piperazinyl, piperidinyl and pyrrolidinyl each of which is substituted with one or more Z substituents which are independently selected, or wherein two Z substitutents on adjacent carbon atoms, on a carbon atom and an adjacent nitrogen atom, or on a single carbon atom, together with the carbon atom(s) and/or the combination of the carbon atom and the adjacent nitrogen atom to which said Z substituents are attached form a four to seven-membered cycloalkyl or heterocyclyl ring.
15. The compound of claim 1 , wherein:
A is —N(R 5 )—;
R 2 is H or —(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl; and
R 5 is H or —(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl.
16. The compound of claim 1 , wherein:
A 2 is a covalent bond; and
R 2 is H or halogen.
17. The compound of claim 1 , wherein:
A 1 is a covalent bond;
R 1 is selected from the group consisting of unsubstituted piperazinyl, unsubstituted piperidinyl, unsubstituted pyrrolidinyl, and piperazinyl, piperidinyl and pyrrolidinyl each of which is substituted with one or more Z substituents which are independently selected, or wherein two Z substitutents on adjacent carbon atoms, on a carbon atom and an adjacent nitrogen atom, or on a single carbon atom, together with the carbon atom(s) and/or the combination of the carbon atom and the adjacent nitrogen atom to which said Z substituents are attached form a four to seven-membered cycloalkyl or heterocyclyl ring;
A 2 is —N(R 5 )—;
R 2 is H or —(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl; and
R 5 is H or —(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl.
18. The compound of claim 8 , wherein:
R 1 is selected from the group consisting of
19. The compound of claim 1 , wherein:
A 1 is a covalent bond;
R 1 is selected from the group consisting of unsubstituted piperazinyl, unsubstituted piperidinyl, unsubstituted pyrrolidinyl, and piperazinyl, puperidinyl and pyrrolidinyl each of which is substituted with one or more Z substitutents on adjacent carbon atoms, on a carbon atom and an adjacent nitrogen atom, or on a single carbon atom, together with the carbon atom(s) and/or the combination of the carbon atom and the adjacent nitrogen atom to which said Z substituents are attached form a four to seven-membered cycloalkyl or heterocyclyl ring;
A 2 is a covalent bond; and
R 2 is H or halogen. R 2 is H halogen.
20. The compound of claim 19 , wherein:
Z is selected from the group consisting of (C 1 -C 6 )alkyl, (C 6 -C 10 )aryl, -(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl, —(C 1 -C 4 )alkylene-O—(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl, —N(R 8 ) 2 , —(C 1 -C 4 )alkylene-N(R 8 ) 2 , —C(O)OH, —C(O)O—(C 1 -C 6 )alkyl, and —(C 1 -C 6 )alkylene-OH, or wherein two Z substitutents on adjacent carbon atoms, on a carbon atom and an adjacent nitrogen atom, or on a single carbon atom, together with the carbon atom(s) and/or the combination of the carbon atom and the adjacent nitrogen atom to which said Z substituents are attached form a four to seven-membered cycloalkyl or heterocyclyl ring.
21. A purified compound of claim 1 .
22. A compound having the structure of Formula (IA):
wherein A 1 , A 2 , R 1 , R 2 are defined as shown in the Table below:
Structure
A 1
A 2
R 1
R 2
A
covalentbond
—NH—
H
B
—O—
—NH—
H
H
C
covalentbond
—NH—
D
covalentbond
E
covalentbond
—NH—
H
F
covalentbond
—NH—
H
G
covalentbond
—NH—
H
H
covalentbond
—NH—
H
I
covalentbond
—NH—
H
J
covalentbond
—NH—
H
K
covalentbond
—NH—
H
L
covalentbond
covalent bond
H
M
covalentbond
covalent bond
Cl
N
covalentbond
—NH—
O
covalentbond
—NH—
P
covalentbond
—NH—
Q
covalentbond
—NH—
R
covalentbond
covalent bond
H
S
covalentbond
covalent bond
Cl
T
covalentbond
covalent bond
H
U
covalentbond
covalent bond
Cl
V
covalentbond
covalent bond
H
W
covalentbond
covalent bond
Cl
X
covalentbond
covalent bond
Cl
Y
covalentbond
covalent bond
H
Z
covalentbond
covalent bond
H
AA
covalentbond
covalent bond
H
AB
covalentbond
covalent bond
H
AC
covalentbond
covalent bond
H
AD
covalentbond
covalent bond
Cl
AE
covalentbond
covalent bond
Cl
AF
covalentbond
covalent bond
H
AG
covalentbond
covalent bond
Cl
AH
covalentbond
covalent bond
H
AI
covalentbond
covalent bond
Cl
AJ
covalentbond
covalent bond
H
AK
covalentbond
covalent bond
Cl
AL
covalentbond
covalent bond
H
AM
covalentbond
covalent bond
Cl
AN
covalentbond
covalent bond
H
AO
covalentbond
covalent bond
H
AP
covalentbond
covalent bond
Cl
AQ
covalentbond
covalent bond
H
AR
covalentbond
covalent bond
H
AS
covalentbond
covalent bond
H
AT
covalentbond
covalent bond
H
AU
covalentbond
covalent bond
H
AV
covalentbond
covalent bond
H
AW
covalentbond
covalent bond
H
AX
covalentbond
covalent bond
H
AY
covalentbond
covalent bond
H
AZ
covalentbond
covalent bond
H
AAA
covalentbond
covalent bond
H
AAB
covalentbond
covalent bond
H
AAC
covalentbond
covalent bond
H
AAD
covalentbond
covalent bond
H
AAE
covalentbond
covalent bond
H
AAF
covalentbond
covalent bond
H
AAG
covalentbond
covalent bond
H
AAH
covalentbond
covalent bond
H
AAI
covalentbond
covalent bond
H
AAJ
covalentbond
covalent bond
H
AAK
covalentbond
covalent bond
H
AAL
covalentbond
—NH—
H
AAM
covalentbond
—NH—
H
AAN
covalentbond
—NH—
H
AAO
covalentbond
—NH—
H
AAP
covalentbond
—NH—
H
AAQ
covalentbond
—NH—
H
AAR
covalentbond
—NH—
H
AAT
covalentbond
—NH—
H
AAU
covalentbond
—NH—
H
AAV
covalentbond
covalent bond
—CH 2 CH 2 -phenyl
AAW
covalentbond
covalent bond
—CH 2 CH 2 -phenyl
AAX
covalentbond
covalent bond
—CH 2 CH 2 -phenyl
AAY
covalentbond
—NH—
AAZ
covalentbond
—NH—
AAAA
covalentbond
—NH—
AAAB
covalentbond
—NH—
AAAC
covalentbond
AAAD
covalentbond
AAAE
covalentbond
—NH—
AAAF
covalentbond
—NH—
AAAG
covalentbond
AAAH
covalentbond
—NH—
AAAI
covalentbond
—NH—
AAAJ
covalentbond
AAAK
covalentbond
—NH—
AAAL
covalentbond
—NH—
or a pharmaceutically acceptable salt thereof.
23. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
24. The compound of claim 23 , selected from the group consisting of:
or a pharmaceutically acceptable thereof.
25. The compound of claim 24 , wherein said compound is
or a pharmaceutically acceptable salt thereof.
26. A pharmaceutical composition comprising:
a compound of claim 1 , or a pharmaceutically acceptable salt thereof; and
at least one pharmaceutically acceptable carrier.
27. A pharmaceutical composition comprising:
a compound of claim 12 , or a pharmaceutically acceptable salt thereof; and
at least one pharmaceutically acceptable carrier.
28. A method of treating a disease, disorder, or condition comprising:
administering to a patient in need thereof a therapeutically effective amount of at least one compound of claim 1 , or a pharmaceutically acceptable salt thereof;
wherein said disease, disorder, or condition is breast cancer.
29. The method of claim 28 , further comprising administering at least one additional active ingredient selected from the group consisting of a second kinase inhibitor, an estrogen receptor modulator, an androgen receptor modulator, a retinoid receptor modulator, a cyctotoxic agent, a prenyl-protein transferase inhibitor, an HMG-CoA reductase inhibitor, an HIV protease inhibitor, a reverse transcriptase inhibitor, an angiogenesis inhibitor, an inhibitor of inherent multidrug resistance, an anti-emetic agent, an agent useful in the treatment of anemia, an agent useful in the treatment of neutropenia, and an immunologic-enhancing agent.
30. A pharmaceutical composition comprising:
a compound of claim 22 , or a pharmaceutically acceptable salt thereof; and
at least one pharmaceutically acceptable carrier.
31. A pharmaceutical composition comprising:
a compound of claim 23 , or a pharmaceutically acceptable salt thereof; and
at least one pharmaceutically acceptable carrier.
32. A method of treating a disease, disorder, or condition comprising: administering to a patient in need thereof a therapeutically effective amount of at least one compound of claim 1 , or a pharmaceutically acceptable salt thereof; wherein said disease, disorder or condition is selected from the group consisting of: ovarian tumor, pancreatic cancer, and prostrate cancer.
33. A method of treating a disease, disorder, or condition comprising: administering to a patient in need thereof a therapeutically effective amount of at least one compound of claim 22 , or a pharmaceutically acceptable salt thereof; wherein said disease, disorder or condition is selected from the group consisting of: ovarian tumor, pancreatic cancer, and prostrate cancer.
34. A method of treating a disease, disorder, or condition comprising:
administering to a patient in need thereof a therapeutically effective amount of at least one compound of claim 23 , or a pharmaceutically acceptable salt thereof; wherein said disease, disorder or condition is selected from the group consisting of: ovarian tumor, pancreatic cancer, and prostrate cancer.
35. The method of claim 32 , further comprising administering at least one additional active ingredient selected from the group consisting of a second kinase inhibitor, an estrogen receptor modulator, an androgen receptor modulator, a retinoid receptor modulator, a cyctotoxic agent, a prenyl-protein transferase inhibitor, an HMG-CoA reductase inhibitor, an HIV protease inhibitor, a reverse transcriptase inhibitor, an angiogenesis inhibitor, an inhibitor of inherent multidrug resistance, an anti-emetic agent, an agent useful in the treatment of anemia, an agent useful in the treatment of neutropenia, and an immunologic-enhancing agent.