Compounds and methods for treating cancer

Patent metadata

Field	Value
Publication number	US-10464897-B2
Application number	US-201615577845-A
Country	US
Kind code	B2
Filing date	Jun 3, 2016
Priority date	Jun 5, 2015
Publication date	Nov 5, 2019
Grant date	Nov 5, 2019

Abstract

The present application relates to compounds comprising an ester, a thioester, or a hydrazide moiety and methods of synthesizing these compounds. The present application also relates to pharmaceutical compositions containing the compounds and methods of treating cell proliferative disorders mediated by the Hh signaling pathway, such as cancer, by administering the compounds and pharmaceutical compositions to subjects in need thereof.

First claim

The invention claimed is:

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:
Z 1 -Z 2 is C(O)—O or O—C(O);
n1 is 0, 1, 2, 3, or 4;
each R 11 is independently halogen, OH, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkoxy, C(O)OH, C(O)-(unsubstituted or substituted C 1 -C 6 alkyl), C(O)-(unsubstituted or substituted C 1 -C 6 alkoxy), C(O)NH-(unsubstituted or substituted C 1 -C 6 alkyl), S(O) p1 -(unsubstituted or substituted C 1 -C 6 alkyl), unsubstituted or substituted C 3 -C 8 cycloalkyl, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heterocyclyl comprising one or two 5- to 8-membered rings and 1-4 heteroatoms selected from O, N, and S, or unsubstituted or substituted heteroaryl comprising one or two 5- to 8-membered rings and 1-4 heteroatoms selected from O, N, and S;
m1 is 0, 1, 2, 3, or 4;
each R 12 is independently halogen, OH, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkoxy, or C(O)-(unsubstituted or substituted C 1 -C 6 alkyl);
o1 is 0, 1, 2, 3, 4, or 5;
each R 13 is independently Cl, Br, OH, unsubstituted or substituted C 1 -C 6 alkyl, substituted C 1 -C 6 alkoxy, C(O)-(unsubstituted or substituted C 1 -C 6 alkyl), or S(O) p1 -(unsubstituted or substituted C 1 -C 6 alkyl); and
p1 is 0, 1, or 2.

2. The compound of claim 1 , having formula Ia:

or a pharmaceutically acceptable salt thereof, wherein Z 3 is O.

3. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

4. The compound of claim 1 , wherein n1 is 0.

5. The compound of claim 1 , wherein at least one R 12 is halogen.

6. The compound of claim 1 , wherein at least one R 12 is Cl.

7. The compound of claim 1 , wherein at least one R 13 is S(O) p1 -(unsubstituted or substituted C 1 -C 6 alkyl).

8. The compound of claim 1 , wherein at least one R 13 is S(O) 2 -(unsubstituted or substituted C 1 -C 6 alkyl).

9. The compound of claim 1 , wherein at least one R 13 is halogen.

10. The compound of claim 1 , wherein at least one R 13 is Cl.

11. The compound of claim 2 , wherein R 12 is halogen.

12. The compound of claim 2 , wherein R 12 is Cl.

13. The compound of claim 2 , wherein at least one R 13 is S(O) p1 -(unsubstituted or substituted C 1 -C 6 alkyl).

14. The compound of claim 2 , wherein at least one R 13 is S(O) 2 -(unsubstituted or substituted C 1 -C 6 alkyl).

15. The compound of claim 2 , wherein at least one R 13 is halogen.

16. The compound of claim 2 , wherein at least one R 13 is Cl.

17. The compound of claim 1 , having the chemical structure selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

Assignees

• Dana Farber Cancer Inst Inc

Inventors

• Bradner James
• Erb Michael
• Qi Jun

Classifications

• C07D413/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D239/78

  with hetero atoms directly attached in position 2 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title