US2018244631A1PendingUtilityA1
Inhibition of olig2 activity
Assignee: CURTANA PHARMACEUTICALS INCPriority: Feb 27, 2015Filed: Feb 26, 2016Published: Aug 30, 2018
Est. expiryFeb 27, 2035(~8.6 yrs left)· nominal 20-yr term from priority
Inventors:Graham BeatonFabio TucciSatheesh B. RavulaStanton MchardyFrancisco Xavier RuizAmbrosio Lopez, Jr.Bismarck CamposHua Wang
A61P 43/00A61P 35/02A61P 35/00C07D 401/12A61P 25/28C07D 239/48C07D 403/12C07D 401/14C07D 403/04C07D 405/12A61K 31/506C07D 413/04A61K 31/17C07D 401/04A61K 31/505
48
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Claims
Abstract
Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of Olig2. Also described herein are methods of using such Olig2 inhibitors, alone and in combination with other compounds, for treating cancer and other diseases. In particular the Olig2 inhibitors may be used to treat glioblastoma.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound having the structure of Formula (I):
wherein:
A is a bond, O, or N(R 10 );
X, Y, and Z are each independently N, or C(R 7 ) wherein at least one of X, Y, and Z are N;
each R 1 is independently halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —CF 3 , —SR 8 , —N(R 8 )S(═O) 2 R 9 , —S(═O) 2 N(R 8 ) 2 , —S(═O)R 9 , —S(═O) 2 R 9 , —C(═O)R 9 , —CO 2 R 8 , —N(R 8 ) 2 , —C(═O)N(R 8 ) 2 , —N(R 8 )C(═O)R 9 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl; or two R 1 are taken together to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted carbocyclic ring;
R 2 and R 3 are each independently H, —CN, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or C 2 -C 7 heterocycloalkyl; or R 2 and R 3 are taken together to form a 5- or 6-membered heterocyclic ring;
R 5 is halogen, —CN, —OH, —CF 3 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl;
R 6 is substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 2 -C 7 heteroaryl, —(C(R 14 )(R 15 )) m R 21 , —(C(R 14 )(R 15 )) m N(R 11 )(R 12 ), or
R 11 and R 12 are each independently H, or substituted or unsubstituted C 1 -C 6 alkyl; or R 11 and R 12 are taken together to form a 5-, 6-, 7-, or 8-membered heterocyclic ring;
J is C(H), or N;
R 13 is H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted —C 1 -C 4 alkylC 6 -C 10 aryl, or substituted or unsubstituted —C 1 -C 4 alkylC 2 -C 7 heteroaryl;
each R 7 is independently H, halogen, —CN, —OH, —CF 3 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl;
each R 14 and R 15 are each independently H, or substituted or unsubstituted C 1 -C 6 alkyl; or
R 14 and R 15 are taken together to form a 4-, 5-, 6-membered cycloalkyl ring;
R 21 is halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —CF 3 , —SR 22 , —N(R 22 )S(═O) 2 R 23 , —S(═O) 2 N(R 22 ) 2 , —S(═O)R 23 , —S(═O) 2 R 23 , —C(═O)R 23 , —CO 2 R 22 , —C(═O)N(R 22 ) 2 , —N(R 22 )C(═O)R 23 , substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl;
each R 22 is independently H, or substituted or unsubstituted C 1 -C 6 alkyl;
R 23 is substituted or unsubstituted C 1 -C 6 alkyl;
each R 8 is independently H, or substituted or unsubstituted C 1 -C 6 alkyl;
R 9 is substituted or unsubstituted C 1 -C 6 alkyl;
R 10 is H or unsubstituted C 1 -C 4 alkyl;
m is 2-6;
n is 0-5;
p is 1-3;
q is 1-3; or
a pharmaceutically acceptable salt, solvate, or prodrug thereof.
2 . The compound of claim 1 , wherein R 2 and R 3 are each independently H, —CN, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or C 2 -C 7 heterocycloalkyl.
3 . The compound of claim 2 , wherein R 2 and R 3 are each H.
4 . The compound of claim 1 , wherein R 2 and R 3 are taken together to form a 5- or 6-membered heterocyclic ring.
5 . The compound of claim 4 , wherein R 2 and R 3 are taken together to form a 5-membered heterocyclic ring.
6 . The compound of any one of claims 1 - 5 , wherein R 6 is substituted or unsubstituted C 2 -C 7 heteroaryl.
7 . The compound of claim 6 , wherein R 6 is substituted or unsubstituted pyridyl.
8 . The compound of claim 7 , wherein R 6 is unsubstituted pyridyl.
9 . The compound of any one of claims 1 - 5 , wherein R 6 is
10 . The compound of claim 9 , wherein R 13 is H.
11 . The compound of claim 9 , wherein R 13 is substituted or unsubstituted C 1 -C 6 alkyl.
12 . The compound of claim 11 , wherein R 13 is —CH 3 .
13 . The compound of claim 11 , wherein R 13 is —CH 2 CH 3 .
14 . The compound of any one of claims 9 - 13 , wherein J is C(H).
15 . The compound of claim 14 , wherein p is 2 and q is 1.
16 . The compound of claim 14 , wherein p is 3 and q is 1.
17 . The compound of claim 14 , wherein p is 2 and q is 2.
18 . The compound of any one of claims 9 - 13 , wherein J is N.
19 . The compound of claim 18 , wherein p is 2 and q is 2.
20 . The compound of any one of claims 1 - 5 , wherein R 6 is substituted or unsubstituted C 2 -C 7 heterocycloalkyl.
21 . The compound of claim 20 , wherein R 6 is substituted or unsubstituted morpholinyl.
22 . The compound of claim 20 , wherein R 6 is substituted or unsubstituted piperidinyl.
23 . The compound of any one of claims 1 - 5 , wherein R 6 is —(C(R 14 )(R 15 )) m R 21 .
24 . The compound of claim 23 , wherein R 21 is —OH.
25 . The compound of any one of claims 1 - 5 , wherein R 6 is —(C(R 14 )(R 15 )) m N(R 11 )(R 12 ).
26 . The compound of claim 25 , wherein R 11 and R 12 are each CH 3 .
27 . The compound of any one of claims 23 - 26 , wherein R 14 and R 15 are each H.
28 . The compound of any one of claims 23 - 27 , wherein m is 2.
29 . The compound of any one of claims 23 - 27 , wherein m is 3.
30 . The compound of any one of claims 1 - 29 , wherein A is N(R 10 ).
31 . The compound of claim 30 , wherein R 10 is H or CH 3 .
32 . The compound of any one of claims 1 - 29 , wherein A is O.
33 . The compound of any one of claims 1 - 29 , wherein A is a bond.
34 . The compound of any one of claims 1 - 33 , wherein R 5 is substituted or unsubstituted C 1 -C 6 alkyl.
35 . The compound of claim 34 , wherein R 5 is CH 3 .
36 . The compound of claim 34 , wherein R 5 is CH 2 CH 3 .
37 . The compound of any one of claims 1 - 36 , wherein n is 2.
38 . The compound of any one of claims 1 - 36 , wherein n is 1.
39 . The compound of any one of claims 1 - 36 , wherein n is O.
40 . The compound of any one of claims 1 - 38 , wherein each R 1 is independently halogen, —CN, —NO 2 , —OH, —CF 3 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl.
41 . The compound of claim 40 , wherein each R 1 is independently halogen, —CN, —OH, —CF 3 , substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 1 -C 6 alkoxy.
42 . The compound of any one of claims 1 - 37 , wherein two R 1 are taken together to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted carbocyclic ring.
43 . The compound of any one of claims 1 - 42 , wherein X is C(R 7 ); Y is N; and Z is N.
44 . The compound of any one of claims 1 - 42 , wherein X is C(R 7 ); Y is C(R 7 ); and Z is N.
45 . The compound of any one of claims 1 - 42 , wherein X is C(R 7 ); Y is N; and Z is C(R 7 ).
46 . The compound of any one of claims 1 - 42 , wherein X is C(R 7 ); Y is C(R 7 ); and Z is C(R 7 ).
47 . The compound of any one of claims 1 - 46 , wherein R 7 is H.
48 . A compound having the structure of Formula (II):
wherein:
each R 1 is independently halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —CF 3 , —SR 8 , —N(R 8 )S(═O) 2 R 9 , —S(═O) 2 N(R 8 ) 2 , —S(═O)R 9 , —S(═O) 2 R 9 , —C(═O)R 9 , —CO 2 R 8 , —N(R 8 ) 2 , —C(═O)N(R 8 ) 2 , —N(R 8 )C(═O)R 9 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl; or two R 1 are taken together to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted carbocyclic ring;
R 2 and R 3 are each independently H, —CN, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or C 2 -C 7 heterocycloalkyl; or R 2 and R 3 are taken together to form a 5- or 6-membered heterocyclic ring;
R 5 is halogen, —CN, —OH, —CF 3 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl;
R 6 is substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 2 -C 7 heteroaryl, —(C(R 14 )(R 15 )) m R 21 , or
J is C(H);
R 13 is H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted —C 1 -C 4 alkylC 6 -C 10 aryl, or substituted or unsubstituted —C 1 -C 4 alkylC 2 -C 7 heteroaryl;
each R 14 and R 15 are each independently H, or substituted or unsubstituted C 1 -C 6 alkyl; or
R 14 and R 15 are taken together to form a 4-, 5-, 6-membered cycloalkyl ring;
R 21 is halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —CF 3 , —SR 22 , —N(R 22 )S(═O) 2 R 23 , —S(═O) 2 N(R 22 ) 2 , —S(═O)R 23 , —S(═O) 2 R 23 , —C(═O)R 23 , —CO 2 R 22 , —C(═O)N(R 22 ) 2 , —N(R 22 )C(═O)R 23 , substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl;
each R 22 is independently H, or substituted or unsubstituted C 1 -C 6 alkyl;
R 23 is substituted or unsubstituted C 1 -C 6 alkyl;
each R 8 is independently H, or substituted or unsubstituted C 1 -C 6 alkyl;
R 9 is substituted or unsubstituted C 1 -C 6 alkyl;
R 10 is H or unsubstituted C 1 -C 4 alkyl;
m is 2-6;
n is 0-5;
p is 1-3;
q is 1-3; or
a pharmaceutically acceptable salt, solvate, or prodrug thereof.
49 . The compound of claim 48 , wherein R 2 and R 3 are each independently H, —CN, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or C 2 -C 7 heterocycloalkyl.
50 . The compound of claim 49 , wherein R 2 and R 3 are each H.
51 . The compound of claim 48 , wherein R 2 and R 3 are taken together to form a 5- or 6-membered heterocyclic ring.
52 . The compound of claim 51 , wherein R 2 and R 3 are taken together to form a 5-membered heterocyclic ring.
53 . The compound of any one of claims 48 - 52 , wherein R 6 is —(C(R 14 )(R 15 )) m R 21 .
54 . The compound of any one of claims 48 - 53 , wherein R 21 is —OH, —N(R 22 )S(═O) 2 R 23 , —CO 2 R 22 , —C(═O)N(R 22 ) 2 , —N(R 22 )C(═O)R 23 , substituted or unsubstituted C 1 -C 6 alkoxy, or substituted or unsubstituted C 2 -C 7 heteroaryl.
55 . The compound of claim 54 , wherein R 21 is —OH.
56 . The compound of claim 54 , wherein R 21 is —N(R 22 )S(═O) 2 R 23 .
57 . The compound of claim 54 , wherein R 21 is —N(R 22 )C(═O)R 23 .
58 . The compound of claim 54 , wherein R 21 is substituted or unsubstituted C 1 -C 6 alkoxy.
59 . The compound of claim 54 , wherein R 21 is substituted or unsubstituted C 2 -C 7 heteroaryl.
60 . The compound of any one of claims 48 - 59 , wherein each R 22 is independently H or unsubstituted C 1 -C 6 alkyl; and R 23 is unsubstituted C 1 -C 6 alkyl.
61 . The compound of any one of claims 48 - 60 , wherein R 14 and R 15 are each independently H, or substituted or unsubstituted C 1 -C 6 alkyl.
62 . The compound of any one of claims 48 - 60 , wherein R 14 and R 15 are each H.
63 . The compound of any one of claims 48 - 62 , wherein m is 2.
64 . The compound of any one of claims 48 - 62 , wherein m is 3.
65 . The compound of any one of claims 48 - 52 , wherein R 6 is substituted or unsubstituted C 2 -C 7 heteroaryl.
66 . The compound of claim 65 , wherein R 6 is substituted or unsubstituted pyridyl.
67 . The compound of any one of claims 48 - 52 , wherein R 6 is substituted or unsubstituted C 2 -C 7 heterocycloalkyl.
68 . The compound of claim 67 , wherein R 6 is substituted or unsubstituted morpholinyl.
69 . The compound of claim 67 , wherein R 6 is substituted or unsubstituted piperidinyl.
70 . The compound of any one of claims 48 - 69 , wherein R 10 is H or CH 3 .
71 . A compound having the structure of Formula (IIA):
wherein:
each R 1 is independently halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —SR 8 , —N(R 8 )S(═O) 2 R 9 , —S(═O) 2 N(R 8 ) 2 , —S(═O)R 9 , —S(═O) 2 R 9 , —C(═O)R 9 , —CO 2 R 8 , —N(R 8 ) 2 , —C(═O)N(R 8 ) 2 , —N(R 8 )C(═O)R 9 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl; or two R 1 are taken together to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted carbocyclic ring;
R 2 and R 3 are each independently H, —CN, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or C 2 -C 7 heterocycloalkyl; or R 2 and R 3 are taken together to form a 5- or 6-membered heterocyclic ring;
R 4 is H, halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —SR 8 , —N(R 8 )S(═O) 2 R 9 , —S(═O) 2 N(R 8 ) 2 , —S(═O)R 9 , —S(═O) 2 R 9 , —C(═O)R 9 , —CO 2 R 8 , —N(R 8 ) 2 , —C(═O)N(R 8 ) 2 , —N(R 8 )C(═O)R 9 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl; or two R 1 are taken together to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted carbocyclic ring; wherein when n is 0, R 4 is not halogen;
R 5 is halogen, —CN, —OH, —CF 3 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl;
R 6 is —(C(R 14 )(R 15 )) m N(R 11 )(R 12 );
R 11 and R 12 are each independently H, or substituted or unsubstituted C 1 -C 6 alkyl; or R 11 and R 12 are taken together to form a 5-, 6-, 7-, or 8-membered heterocyclic ring;
R 13 is H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted —C 1 -C 4 alkylC 6 -C 10 aryl, or substituted or unsubstituted —C 1 -C 4 alkylC 2 -C 7 heteroaryl;
each R 14 and R 15 are each independently H, or substituted or unsubstituted C 1 -C 6 alkyl; or
R 14 and R 15 are taken together to form a 4-, 5-, 6-membered cycloalkyl ring;
each R 8 is independently H, or substituted or unsubstituted C 1 -C 6 alkyl;
R 9 is substituted or unsubstituted C 1 -C 6 alkyl;
R 10 is H, or C 1 -C 4 alkyl;
m is 2-6;
n is 0-4; or
a pharmaceutically acceptable salt, solvate, or prodrug thereof.
72 . The compound of claim 71 , wherein R 2 and R 3 are each independently H, —CN, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or C 2 -C 7 heterocycloalkyl.
73 . The compound of claim 72 , wherein R 2 and R 3 are each H.
74 . The compound of claim 71 , wherein R 2 and R 3 are taken together to form a 5- or 6-membered heterocyclic ring.
75 . The compound of claim 74 , wherein R 2 and R 3 are taken together to form a 5-membered heterocyclic ring.
76 . The compound of any one of claims 71 - 75 , wherein R 6 is —(C(R 14 )(R 15 )) m N(R 11 )(R 12 ) and R 14 and R 15 are each H.
77 . The compound of claim 76 , wherein R 11 and R 12 are each independently H, or substituted or unsubstituted C 1 -C 6 alkyl.
78 . The compound of claim 77 , wherein R 11 and R 12 are each independently unsubstituted C 1 -C 6 alkyl.
79 . The compound of claim 78 , wherein R 11 and R 12 are each —CH 3 .
80 . The compound of any one of claims 71 - 79 , wherein m is 2.
81 . The compound of any one of claims 71 - 79 , wherein m is 3.
82 . The compound of any one of claims 71 - 81 , wherein R 10 is H or CH 3 .
83 . The compound of any one of claims 71 - 82 , wherein n is O.
84 . The compound of any one of claims 71 - 82 , wherein n is 1.
85 . A compound having the structure of Formula (VI):
wherein:
each R 1 is independently halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —CF 3 , —SR 8 , —N(R 8 )S(═O) 2 R 9 , —S(═O) 2 N(R 8 ) 2 , —S(═O)R 9 , —S(═O) 2 R 9 , —C(═O)R 9 , —CO 2 R 8 , —N(R 8 ) 2 , —C(═O)N(R 8 ) 2 , —N(R 8 )C(═O)R 9 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 —C cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, or substituted or unsubstituted C 2 -C 7 heteroaryl; or two R 1 are taken together to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted carbocyclic ring;
R 2 and R 3 are each independently H or C 1 -C 4 alkyl; or R 2 and R 3 are taken together to form a 5- or 6-membered heterocyclic ring;
R 5 is substituted or unsubstituted C 1 -C 6 alkyl;
R 6 is unsubstituted C 1 -C 4 alkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 —C cycloalkyl, substituted or unsubstituted C 2 -C 7 heteroaryl, —(C(R 14 )(R 15 )) m R 21 ,
J is C(H);
R 13 is H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted —C 1 -C 4 alkylC 6 -C 10 aryl, or substituted or unsubstituted —C 1 -C 4 alkylC 2 -C 7 heteroaryl;
each R 14 and R 15 are each independently H, halogen, or substituted or unsubstituted C 1 -C 6 alkyl;
R 21 is halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —CF 3 , —SR 22 , —N(R 22 )S(═O) 2 R 23 , —S(═O) 2 N(R 22 ) 2 , —S(═O)R 23 , —S(═O) 2 R 23 , —C(═O)R 23 , —CO 2 R 22 , —C(═O)NR 22 ) 2 , —N(R 22 )C(═O)R 23 , substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 2 -C 7 heterocycloalkyl, or substituted or unsubstituted C 2 -C 7 heteroaryl;
each R 22 is independently H, or substituted or unsubstituted C 1 -C 6 alkyl;
R 23 is substituted or unsubstituted C 1 -C 6 alkyl;
each R 8 is independently H, or substituted or unsubstituted C 1 -C 6 alkyl;
R 9 is substituted or unsubstituted C 1 -C 6 alkyl;
R 10 is H;
m is 2-6;
n is 0-5;
p is 1-3;
q is 1-3; or
a pharmaceutically acceptable salt, solvate, or prodrug thereof.
86 . The compound of claim 85 , wherein R 2 and R 3 are each independently H or C 1 -C 4 alkyl.
87 . The compound of claim 86 , wherein R 2 and R 3 are each H.
88 . The compound of claim 85 , wherein R 2 and R 3 are taken together to form a 5- or 6-membered heterocyclic ring.
89 . The compound of claim 88 , wherein R 2 and R 3 are taken together to form a 5-membered heterocyclic ring.
90 . The compound of any one of claims 85 - 89 , wherein R 6 is —(C(R 14 )(R 15 )) m R 21 .
91 . The compound of any one of claims 85 - 90 , wherein each R 14 and R 15 are each independently H, halogen, or unsubstituted C 1 -C 6 alkyl.
92 . The compound of any one of claims 85 - 90 , wherein R 14 and R 15 are each H.
93 . The compound of any one of claims 85 - 92 , wherein R 21 is —OH, —N(R 22 )S(═O) 2 R 23 , —CO 2 R 22 , —C(═O)N(R 22 ) 2 , —N(R 22 )C(═O)R 23 , substituted or unsubstituted C 1 -C 6 alkoxy, or substituted or unsubstituted C 2 -C 7 heteroaryl.
94 . The compound of claim 93 , wherein R 21 is —OH.
95 . The compound of claim 93 , wherein R 21 is —N(R 22 )S(═O) 2 R 23 .
96 . The compound of claim 93 , wherein R 21 is —N(R 22 )C(═O)R 23 .
97 . The compound of claim 93 , wherein R 21 is substituted or unsubstituted C 1 -C 6 alkoxy.
98 . The compound of claim 93 , wherein R 21 is substituted or unsubstituted C 2 -C 7 heteroaryl.
99 . The compound of any one of claims 85 - 98 , wherein each R 22 is independently H or unsubstituted C 1 -C 6 alkyl; and R 23 is unsubstituted C 1 -C 6 alkyl.
100 . The compound of any one of claims 85 - 99 , wherein m is 2.
101 . The compound of any one of claims 85 - 99 , wherein m is 3.
102 . The compound of any one of claims 85 - 89 , wherein R 6 is
103 . The compound of any one of claims 85 - 89 , wherein R 6 is
104 . The compound of claim 102 or 103 , wherein R 13 is H or unsubstituted C 1 -C 6 alkyl.
105 . The compound of any one of claims 85 - 104 , wherein each R 1 is independently halogen, —OCF 3 , —CF 3 , unsubstituted C 1 -C 6 alkyl, or unsubstituted C 1 -C 6 alkoxy.
106 . The compound of any one of claims 85 - 104 , wherein each R 1 is independently halogen.
107 . The compound of any one of claims 85 - 106 , wherein n is 1.
108 . The compound of any one of claims 85 - 106 , wherein n is 2.
109 . The compound of any one of claims 85 - 104 , wherein n is O.
110 . A compound having a structure selected from:
or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
111 . A pharmaceutical composition comprising a compound of any one of claims 1 - 110 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and at least one pharmaceutically acceptable excipient.
112 . A method for treating a disease in a subject comprising administering to the subject in need thereof a composition comprising a compound of any one of claims 1 - 110 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof; wherein the disease is cancer or Down's Syndrome.
113 . The method of claim 112 , wherein the disease is cancer.
114 . The method of claim 113 , wherein the cancer is brain cancer, glioblastoma multiforme, medulloblastoma, astrocytomas, brain stem gliomas, meningiomas, oligodendrogliomas, melanoma, lung cancer, breast cancer, or leukemia.
115 . The method of claim 112 , wherein the disease is Down's Syndrome.
116 . A method for inhibiting the activity of Olig2 in a cell comprising contacting the cell with a compound of any one of claims 1 - 110 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof.Join the waitlist — get patent alerts
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