Substituted triphenyl butenes

• US 8,063,249 B1
• Filed: 04/23/2009
• Issued: 11/22/2011
• Est. Priority Date: 04/25/2008
• Status: Expired due to Fees

• Current Assignee: Olema Pharmaceuticals, Inc.
• Original Assignee: Olema Pharmaceuticals, Inc.
• Inventors: Myles, David, Kushner, Peter, Harmon, Cyrus
• Primary Examiner(s): Davis; Brian J
• Application Number:
  US12/429,128
• Time in Patent Office: 943 Days
• Field of Search: None
• US Class Current: 564/324
• CPC Class Codes: C07C 317/28 with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
• CPC Class Codes: C07C 323/12 the carbon skeleton being acyclic and saturated

Abstract

The present invention is directed to compounds, compositions thereof, and the use of the compounds and compositions for the treatment and prevention of breast cancer. In one embodiment, the present invention relates to the use of a substituted triphenyl butene or prodrug thereof for the treatment of breast cancer in mono-therapy or in combination therapy, or for a reduction in the recurrence rate of previously-treated breast cancer.

Claims

1. A compound of formula I or formula II:

2. A compound according to claim 1, wherein R₃ is selected from perfluoromethyl and perfluoroethyl.

7. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

8. A composition according to claim 7, wherein the compound is optically active, and wherein the composition further comprises an enantiomer of said compound, and further wherein the compound and its enantiomer are present in an equimolar ratio.

9. A composition comprising a compound of claim 1,

which compound is in a form selected from the group consisting of an anhydrous form, a single crystalline form, a mixture of polymorphic forms, and mixtures thereof.

10. A composition comprising a mixture of compounds according to claim 1, wherein the mixture comprises a compound according to Formula I and a compound according to Formula II, wherein said compounds are E/Z isomers of each other.

11. A composition according to claim 10, wherein the E/Z isomers are present in an equimolar ratio.

12. A method of treating breast cancer in a human in need thereof comprising administering a compound according to claim 1 to a human.

13. A method according to claim 12, wherein the human is female.

14. A method according to claim 13, wherein the female exhibits reduced metabolism of tamoxifen.

15. The method according to claim 12, further comprising administration of one or more anti-cancer agents.

16. The method according to claim 12, wherein the breast cancer is ER-positive.

17. A method of reducing the risk of recurrence of breast cancer in a human previously treated for breast cancer comprising administering a compound according to claim 1 to said human.

3. A compound of formula I or formula II:

4. A compound according to claim 3, wherein Y is —

R₄OR₅—

or —

R₄NR₂R₅—

.

5. A compound according to claim 4, wherein n is an integer from 2 to 4.

6. A compound selected from the group consisting of