US2005130977A1PendingUtilityA1
Inhibitors of akt activity
Priority: Apr 8, 2002Filed: Apr 4, 2003Published: Jun 16, 2005
Est. expiryApr 8, 2022(expired)· nominal 20-yr term from priority
C07D 403/12C07D 241/42C07D 401/12A61P 35/00C07D 409/12C07D 417/12A61P 43/00C07D 471/04
47
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Claims
Abstract
The present invention is directed to compounds comprising a 2,3-diphenylquinoxaline moiety which inhibit the activity of Akt, a serine/threonine protein kinase. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for treating cancer comprising administration of the compounds of the invention.
Claims
exact text as granted — not AI-modified1 . A compound of the Formula A:
wherein:
a is 0 or 1;
b is 0 or 1;
m is 0, 1 or 2;
n is 0, 1, 2 or 3;
p is 0, 1 or 2;
r is 0 or 1;
s is 0 or 1;
t is 2, 3, 4, 5 or 6;
u, v, w and x are independently selected from: CH and N;
y and z are independently selected from: CH and N, provided that at least one of y and z is N;
R 1 is independently selected from:
1) (C═O) a O b C 1 -C 10 alkyl,
2) (C═O) a O b aryl,
3) C 2 -C 10 alkenyl,
4) C 2 -C 10 alkynyl,
5) (C═O) a O b heterocyclyl,
6) (C═O) a O b C 3 -C 8 cycloalkyl,
7) CO 2 H,
8) halo,
9) CN,
10) OH,
11) O b C 1 -C 6 perfluoroalkyl,
12) O a (C═O) b NR 7 R 8 ,
13) NR c (C═O)NR 7 R 8 ,
14) S(O) m R a ,
15) S(O) 2 NR 7 R 8 ,
16) NR c S(O) m R a ,
17) oxo,
18) CHO,
19) NO 2 ,
20) NR c (C═O)O b R a ,
21) O(C═O)O b C 1 -C 10 alkyl,
22) O(C═O)O b C 3 -C 8 cycloalkyl,
23) O(C═O)O b aryl, and
24) O(C═O)O b -heterocycle,
said alkyl, aryl, alkenyl, alkynyl, heterocyclyl, and cycloalkyl optionally substituted with one or more substituents selected from R z ;
R 2 is independently selected from:
1) (C═O) a O b C 1 -C 10 alkyl,
2) (C═O) a O b aryl,
3) C 2 -C 10 alkenyl,
4) C 2 -C 10 alkynyl,
5) (C═O) a O b heterocyclyl,
6) (C═O) a O b C 3 -C 8 cycloalkyl,
7) CO 2 H,
8) halo,
9) CN,
10) OH,
11) O b C 1 -C 6 perfluoroalkyl,
12) O a (C═O) b NR 7 R 8 ,
13) NR c (C═O)NR 7 R 8 ,
14) S(O) m R a ,
15) S(O) 2 NR 7 R 8 ,
16) NR c S(O) m R a ,
17) CHO,
18) NO 2 ,
19) NR c (C═O)O b R a ,
20) O(C═O)O b C 1 -C 10 alkyl,
21) O(C═O)O b C 3 -C 8 cycloalkyl,
22) O(C═O)O b aryl, and
23) O(C═O)O b -heterocycle,
said alkyl, aryl, alkenyl, alkynyl, heterocyclyl, and cycloalkyl optionally substituted with one, two or three substituents selected from R z ;
R 3 and R 4 are independently selected from: H, C 1 -C 6 -alkyl and C 1 -C 6 -perfluoroalkyl, or
R 3 and R 4 are combined to form —(CH 2 ) t — wherein one of the carbon atoms is optionally replaced by a moiety selected from O, S(O) m , —N(R b )C(O)—, and
—N(COR a )—;
R 5 is independently selected from:
1) H,
2) (C═O)O b C 1 -C 10 alkyl,
3) (C═O)O b C 3 -C 8 cycloalkyl,
4) (C═O)O b aryl,
5) (C═O)O b heterocyclyl,
6) C 1 -C 10 alkyl,
7) aryl,
8) C 2 -C 10 alkenyl,
9) C 2 -C 10 alkynyl,
10) heterocyclyl,
11) C 3 -C 8 cycloalkyl,
12) SO 2 R a , and
13) (C═O)NR b 2 ,
said alkyl, cycloalkyl, aryl, heterocyclyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R z ;
R 6 is NR 7 R 8 , (C 1 -C 6 )alkyl, (C 1 -C 6 )perfluoroalkyl, (C 3 -C 6 )cycloalkyl, noboranyl, aryl, 2,2,2-trifluoroethyl, benzyl or heterocyclyl, said alkyl, cycloalkyl, noboranyl, aryl, heterocyclyl and benzyl is optionally substituted with one or more substituents selected from R z ;
R 7 and R 8 are independently selected from:
1) H,
2) (C═O)O b C 1 -C 10 alkyl,
3) (C═O)O b C 3 -C 8 cycloalkyl,
4) (C═O)O b aryl,
5) (C═O)O b heterocyclyl,
6) C 1 -C 10 alkyl,
7) aryl,
8) C 2 -C 10 alkenyl,
9) C 2 -C 10 alkynyl,
10) heterocyclyl,
11) C 3 -Cg cycloalkyl,
12) SO 2 R a , and
13) (C═O)NR b 2 ,
said alkyl, cycloalkyl, aryl, heterocylyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R z , or
R 7 and R 8 can be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 5-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, said monocyclic or bicyclic heterocycle optionally substituted with one or more substituents selected from R z ;
R z is selected from:
1) (C═O) r O s (C 1 -C 10 )alkyl,
2) O r (C 1 -C 3 )perfluoroalkyl,
3) (C 0 -C 6 )alkylene-S(O) m R a ,
4) oxo,
5) OH,
6) halo,
7) CN,
8) (C═O) r O s (C 2 -C 10 )alkenyl,
9) (C═O) r O s (C 2 -C 10 )alkynyl,
10) (C═O) r O s (C 3 -C 6 )cycloalkyl,
11) (C═O) r O s (C 0 -C 6 )alkylene-aryl,
12) (C═O) r O s (C 0 -C 6 )alkylene-heterocyclyl,
13) (C═O) r O s (C 0 -C 6 )alkylene-N(R b ) 2 ,
14) C(O)R a ,
15) (C 0 -C 6 )alkylene-CO 2 R a ,
16) C(O)H,
17) (C 0 -C 6 )alkylene-CO 2 H,
18) C(O)N(R b ) 2 ,
19) S(O) m R a ,
20) S(O) 2 N(R b ) 2
21) NR c (C═O)O b R a ,
22) O(C═O)O b C 1 -C 10 alkyl,
23) O(C═O)O b C 3 -C 8 cycloalkyl,
24) O(C═O)O b aryl, and
25) O(C═O)O b -heterocycle,
said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heterocyclyl is optionally substituted with up to three substituents selected from R b , OH, (C 1 -C 6 )alkoxy, halogen, CO 2 H, CN, O(C═O)C 1 -C 6 alkyl, oxo, and N(R b ) 2 ;
R a is (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, substituted or unsubstituted aryl, (C 1 -C 6 )perfluoroalkyl, 2,2,2-trifluoroethyl, or substituted or unsubstituted heterocyclyl; and
R b is H, (C 1 -C 6 )alkyl, substituted or unsubstituted aryl, substituted or unsubstituted benzyl, substituted or unsubstituted heterocyclyl, (C 3 -C 6 )cycloalkyl, (C═O)OC 1 -C 6 alkyl, (C═O)C 1 -C 6 alkyl or S(O) 2 R a ;
R c is selected from:
1) H,
2) C 1 -C 10 alkyl,
3) aryl,
4) C 2 -C 10 alkenyl,
5) C 2 -C 10 alkynyl,
6) heterocyclyl,
7) C 3 -C 8 cycloalkyl,
8) C 1 -C 6 perfluoroalkyl,
said alkyl, cycloalkyl, aryl, heterocylyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R z ;
or a pharmaceutically acceptable salt or a stereoisomer thereof.
2 . The compound according to claim 1 of the Formula B:
wherein:
a is 0 or 1;
b is 0 or 1;
m is 0, 1 or 2;
n is 0, 1, 2 or 3;
p is 0, 1 or 2;
r is 0 or 1;
s is 0 or 1;
u, v, w and x are independently selected from: CH and N, provided that only one of u, v, w and x may be N;
R 1 is independently selected from:
1) (C═O) a O b C 1 -C 10 alkyl,
2) (C═O) a O b aryl,
3) C 2 -C 10 alkenyl,
4) C 2 -C 10 alkynyl,
5) (C═O) a O b heterocyclyl,
6) (C═O) a O b C 3 -C 8 cycloalkyl,
7) CO 2 H,
8) halo,
9) CN,
10) OH,
11) O b C 1 -C 6 perfluoroalkyl,
12) O a (C═O) b NR 7 R 8 ,
13) NR c (C═O)NR 7 R 8 ,
14) S(O) m R a ,
15) S(O) 2 NR 7 R 8 ,
16) NR c S(O) m R a ,
17) oxo,
18) CHO,
19) NO 2 ,
20) NR c (C═O)O b R a ,
21) O(C═O)O b C 1 -C 1 O alkyl,
22) O(C═O)O b C 3 -C 8 cycloalkyl,
23) O(C═O)O b aryl, and
24) O(C═O)O b -heterocycle,
said alkyl, aryl, alkenyl, alkynyl, heterocyclyl, and cycloalkyl optionally substituted with one or more substituents selected from R z ;
R 2 is independently selected from:
1) (C═O) a O b C 1 -C 10 alkyl,
2) (C═O) a O b aryl,
3) C 2 -C 10 alkenyl,
4) C 2 -C 10 alkynyl,
5) (C═O) a O b heterocyclyl,
6) (C═O) a O b C 3 -C 8 cycloalkyl,
7) CO 2 H,
8) halo,
9) CN,
10) OH,
11) O b C 1 -C 6 perfluoroalkyl,
12) O a (C═O) b NR 7 R 8 ,
13) NR c (C═O)NR 7 R 8 ,
14) S(O) m R a ,
15) S(O) 2 NR 7 R 8 ,
16) NR c S(O) m R a ,
17) CHO,
18) NO 2 ,
19) NR c (C═O)O b R a ,
20) O(C═O)O b C 1 -C 10 alkyl,
21) O(C═O)O b C 3 -C 8 cycloalkyl,
22) O(C═O)O b aryl, and
23) O(C═O)O b -heterocycle,
said alkyl, aryl, alkenyl, alkynyl, heterocyclyl, and cycloalkyl optionally substituted with one, two or three substituents selected from R z ;
R 5 is independently selected from:
1) H,
2) (C═O)O b C 1 -C 10 alkyl,
3) (C═O)O b C 3 -C 8 cycloalkyl,
4) (C═O)O b aryl,
5) (C═O)O b heterocyclyl,
6) C 1 -C 10 alkyl,
7) aryl,
8) C 2 -C 10 alkenyl,
9) C 2 -C 10 alkynyl,
10) heterocyclyl,
11) C 3 -C 8 cycloalkyl,
12) SO 2 R a , and
13) (C═O)NR b 2 ,
said alkyl, cycloalkyl, aryl, heterocylyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R z ;
R 6 is NR 7 R 8 , (C 1 -C 6 )alkyl, (C 1 -C 6 )perfluoroalkyl, (C 3 -C 6 )cycloalkyl, noboranyl, aryl, 2,2,2-trifluoroethyl, benzyl or heterocyclyl, said alkyl, cycloalkyl, noboranyl, aryl, heterocyclyl and benzyl is optionally substituted with one or more substituents selected from R z ;
R 7 and R 8 are independently selected from:
1) H,
2) (C═O)O b C 1 -C 10 alkyl,
3) (C═O)O b C 3 -C 8 cycloalkyl,
4) (C═O)O b aryl,
5) (C═O)O b heterocyclyl,
6) C 1 -C 10 alkyl,
7) aryl,
8) C 2 -C 10 alkenyl,
9) C 2 -C 10 alkynyl,
10) heterocyclyl,
11) C 3 -C 8 cycloalkyl,
12) SO 2 R a , and
13) (C═O)NR b 2 ,
said alkyl, cycloalkyl, aryl, heterocylyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R z , or
R 7 and R 8 can be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 5-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, said monocyclic or bicyclic heterocycle optionally substituted with one or more substituents selected from R z ;
R z is selected from:
1) (C═O) r O s (C 1 -C 10 )alkyl,
2) O r (C 1 -C 3 )perfluoroalkyl,
3) (C 0 -C 6 )alkylene-S(O) m R a ,
4) oxo,
5) OH,
6) halo,
7) CN,
8) (C═O) r O s (C 2 -C 10 )alkenyl,
9) (C═O) r O s (C 2 -C 10 )alkynyl,
10) (C═O) r O s (C 3 -C 6 )cycloalkyl,
11) (C═O) r O s (C 0 -C 6 )alkylene-aryl,
12) (C═O) r O s (C 0 -C 6 )alkylene-heterocyclyl,
13) (C═O) r O s (C 0 -C 6 )alkylene-N(R b ) 2 ,
14) C(O)R a ,
15) (C 0 -C 6 )alkylene-CO 2 R a ,
16) C(O)H,
17) (C 0 -C 6 )alkylene-CO 2 H,
18) C(O)N(R b ) 2 ,
19) S(O) m R a ,
20) S(O) 2 NR 9 R 10
21) NR c (C═O)O b R a ,
22) O(C═O)O b C 1 -C 10 alkyl,
23) O(C═O)O b C 3 -C 8 cycloalkyl,
24) O(C═O)O b aryl, and
25) O(C═O)O b -heterocycle,
said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heterocyclyl is optionally substituted with up to three substituents selected from R b , OH, (C 1 -C 6 )alkoxy, halogen, CO 2 H, CN, O(C═O)C 1 -C 6 alkyl, oxo, and N(R b ) 2 ;
R a is (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, substituted or unsubstituted aryl, (C 1 -C 6 )perfluoroalkyl, 2,2,2-trifluoroethyl, or substituted or unsubstituted heterocyclyl; and
R b is H, (C 1 -C 6 )alkyl, substituted or unsubstituted aryl, substituted or unsubstituted benzyl, substituted or unsubstituted heterocyclyl, (C 3 -C 6 )cycloalkyl, (C═O)OC 1 -C 6 alkyl, (C═O)C 1 -C 6 alkyl or S(O) 2 R a ;
R c is selected from:
1) H,
2) C 1 -C 10 alkyl,
3) aryl,
4) C 2 -C 10 alkenyl,
5) C 2 -C 10 alkynyl,
6) heterocyclyl,
7) C 3 -C 8 cycloalkyl,
8) C 1 -C 6 perfluoroalkyl,
said alkyl, cycloalkyl, aryl, heterocylyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R z ;
or a pharmaceutically acceptable salt or a stereoisomer thereof.
3 . The compound according to claim 2 of the Formula B:
wherein:
a is 0 or 1;
b is 0 or 1;
m is 0, 1 or 2;
n is 0, 1, 2 or 3;
p is 0, 1 or 2;
r is 0 or 1;
s is 0 or 1;
u, v, w and x are independently selected from: CH and N, provided that only one of u, v, w and x may be N;
R 1 is independently selected from:
1) (C═O) a O b C 1 -C 10 alkyl,
2) (C═O) a O b aryl,
3) C 2 -C 10 alkenyl,
4) C 2 -C 10 alkynyl,
5) (C═O) a O b heterocyclyl,
6) (C═O) a O b C 3 -C 8 cycloalkyl,
7) CO 2 H,
8) halo,
9) CN,
10) OH,
11) O b C 1 -C 6 perfluoroalkyl,
12) O a (C═O) b NR 7 R 8 ,
13) NR c (C═O)NR 7 R 8 ,
14) S(O) m R a ,
15) S(O) 2 NR 7 R 8 ,
16) NR c S(O) m R a ,
17) oxo,
18) CHO,
19) NO 2 ,
20) NR c (C═O)O b R a ,
21) O(C═O)O b C 1 -C 10 alkyl,
22) O(C═O)O b C 3 -C 8 cycloalkyl,
23) O(C═O)O b aryl, and
24) O(C═O)O b -heterocycle,
said alkyl, aryl, alkenyl, alkynyl, heterocyclyl, and cycloalkyl optionally substituted with one or more substituents selected from R z ;
R 2 is independently selected from:
1) C 1 -C 6 alkyl,
2) aryl,
3) heterocyclyl,
4) CO 2 H,
5) halo,
6) CN,
7) OH,
8) S(O) 2 NR 7 R 8 ,
said alkyl, aryl and heterocyclyl optionally substituted with one, two or three substituents selected from R z ;
R 5 is independently selected from:
1) H,
2) C 1 -C 10 alkyl,
3) aryl, and
4) C 3 -C 8 cycloalkyl,
said alkyl, cycloalkyl and aryl is optionally substituted with one or more substituents selected from R z ;
R 6 is NR 7 R 8 , (C 1 -C 6 )alkyl, (C 1 -C 6 )perfluoroalkyl, (C 3 -C 6 )cycloalkyl, noboranyl, aryl, 2,2,2-trifluoroethyl, benzyl or heterocyclyl, said alkyl, cycloalkyl, noboranyl, aryl, heterocyclyl and benzyl is optionally substituted with one or more substituents selected from R z ;
R 7 and R 8 are independently selected from:
1) H,
2) (C═O)O b C 1 -C 10 alkyl,
3) (C═O)O b C 3 -C 8 cycloalkyl,
4) (C═O)O b aryl,
5) (C═O)O b heterocyclyl,
6) C 1 -C 10 alkyl,
7) aryl,
8) C 2 -C 10 alkenyl,
9) C 2 -C 10 alkynyl,
10) heterocyclyl,
11) C 3 -C 8 cycloalkyl,
12) SO 2 R a , and
13) (C═O)NR b 2 ,
said alkyl, cycloalkyl, aryl, heterocylyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R z , or
R z is selected from:
1) (C═O) r O s (C 1 -C 10 )alkyl,
2) O r (C 1 -C 3 )perfluoroalkyl,
3) (C 0 -C 6 )alkylene-S(O) m R a ,
4) oxo,
5) OH,
6) halo,
7) CN,
8) (C═O) r O s (C 2 -C 10 )alkenyl,
9) (C═O) r O s (C 2 -C 10 )alkynyl,
10) (C═O) r O s (C 3 -C 6 )cycloalkyl,
11) (C═O) r O s (C 0 -C 6 )alkylene-aryl,
12) (C═O) r O s (C 0 -C 6 )alkylene-heterocyclyl,
13) (C═O) r O s (C 0 -C 6 )alkylene-N(R b ) 2 ,
14) C(O)R a ,
15) (C 0 -C 6 )alkylene-CO 2 R a ,
16) C(O)H,
17) (C 0 -C 6 )alkylene-CO 2 H,
18) C(O)N(R b ) 2 ,
19) S(O) m R a , and
20) S(O) 2 NR 9 R 10
21) NR c (C═O)O b R a ,
22) O(C═O)O b C 1 -C 10 alkyl,
23) O(C═O)O b C 3 -C 8 cycloalkyl,
24) O(C═O)O b aryl, and
25) O(C═O)O b -heterocycle,
said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heterocyclyl is optionally substituted with up to three substituents selected from R b , OH, (C 1 -C 6 )alkoxy, halogen, CO 2 H, CN, O(C═O)C 1 -C 6 alkyl, oxo, and N(R b ) 2 ;
R a is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, substituted or unsubstituted aryl, or heterocyclyl; and
R b is H, (C 1 -C 6 )alkyl, substituted or unsubstituted aryl, substituted or unsubstituted benzyl, substituted or unsubstituted heterocyclyl, (C 3 -C 6 )cycloalkyl, (C═O)OC 1 -C 6 alkyl, (C═O)C 1 -C 6 alkyl or S(O) 2 R a ;
R c is selected from:
1) H,
2) C 1 -C 10 alkyl,
3) aryl,
4) C 2 -C 10 alkenyl,
5) C 2 -C 10 alkynyl,
6) heterocyclyl,
7) C 3 -C 8 cycloalkyl,
8) C 1 -C 6 perfluoroalkyl,
said alkyl, cycloalkyl, aryl, heterocylyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R z ;
or a pharmaceutically acceptable salt or a stereoisomer thereof.
4 . The compound according to claim 1 which is:
N-[4-(3-phenylquinoxalin-2-yl)benzyl]propane-1-sulfonamide.
5 . The TFA salt according to claim 1 which is:
N-[4-(3-phenylquinoxalin-2-yl)benzyl]propane-1-sulfonamide.
6 . The compound according to claim 1 which is selected from:
R
or a pharmaceutically acceptable salt or a stereoisomer thereof.
7 . The TFA salt according to claim 1 which is selected from:
R
or a stereoisomer thereof.
8 . A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of claim 1 .
9 . A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of claim 4 .
10 . A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of claim 6 .
11 . A method of inhibiting one or more of the isoforms of Akt in a mammal which comprises administering to the mammal a therapeutically effective amount of a compound of claim 1 .
12 . A method of inhibiting one or more of the isoforms of Akt in a mammal which comprises administering to the mammal a therapeutically effective amount of a compound of claim 4 .
13 . A method of inhibiting one or more of the isoforms of Akt in a mammal which comprises administering to the mammal a therapeutically effective amount of a compound of claim 6 .
14 . A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 1 .
15 . A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 4 .
16 . A method for treating cancer which comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 6 .
17 . A pharmaceutical composition made by combining the compound of claim 1 and a pharmaceutically acceptable carrier.
18 . (canceled)
19 . (canceled)
20 . (canceled)
21 . (canceled)
22 . (canceled)
23 . A method of treating or preventing cancer which comprises administering a therapeutically effective amount of a compound of claim 1 in combination with a compound selected from:
1) an estrogen receptor modulator, 2) an androgen receptor modulator, 3) retinoid receptor modulator, 4) a cytotoxic agent, 5) an antiproliferative agent, 6) a prenyl-protein transferase inhibitor, 7) an HMG-CoA reductase inhibitor, 8) an HIV protease inhibitor, 9) a reverse transcriptase inhibitor, 10) an angiogenesis inhibitor, 11) a PPAR-γ agonists, 12) a PPAR-δ agonists, 13) an inhibitor of inherent multidrug resistance, 14) an anti-emetic agent, 15) an agent useful in the treatment of anemia, 16) an agent useful in the treatment of neutropenia, 17) an immunologic-enhancing drug, 18) an inhibitor of cell proliferation and survival signaling, and 19) an agent that interfers with a cell cycle checkpoint.
24 . A method of treating cancer which comprises administering a therapeutically effective amount of a compound of claim 1 in combination with radiation therapy and a compound selected from:
1) an estrogen receptor modulator, 2) an androgen receptor modulator, 3) retinoid receptor modulator, 4) a cytotoxic agent, 5) an antiproliferative agent, 6) a prenyl-protein transferase inhibitor, 7) an HMG-CoA reductase inhibitor, 8) an HIV protease inhibitor, 9) a reverse transcriptase inhibitor, 10) an angiogenesis inhibitor, 11) a PPAR-γ agonists, 12) a PPAR-δ agonists, 13) an inhibitor of inherent multidrug resistance, 14) an anti-emetic agent, 15) an agent useful in the treatment of anemia, 16) an agent useful in the treatment of neutropenia, 17) an immunologic-enhancing drug, 18) an inhibitor of cell proliferation and survival signaling, and 19) an agent that interfers with a cell cycle checkpoint.
25 . (canceled)Join the waitlist — get patent alerts
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