Marinopyrrole derivatives as anticancer agents

Patent metadata

Field	Value
Publication number	US-9340501-B2
Application number	US-201314394902-A
Country	US
Kind code	B2
Filing date	Feb 1, 2013
Priority date	Apr 16, 2012
Publication date	May 17, 2016
Grant date	May 17, 2016

Abstract

Marinopyrrole derivatives and methods for their synthesis and use are described herein. The methods of using the compounds include treating and preventing cancer.

First claim

What is claimed is:

1. A compound of the following structure:

or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R 1 , R 2 , R 3 , and R 4 , are each independently selected from hydrogen, halogen, hydroxyl, cyano, nitro, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkoxyl, substituted or unsubstituted aryloxyl, and substituted or unsubstituted carboxyl;
each R 11 , R 12 , R 13 , and R 14 are F, Cl, Br, or I; and
R 5 and R 6 are each selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, and monovalent cation, and
wherein at least one of R 3 and R 4 is a halogen.

2. The compound of claim 1 , wherein at least one of R 3 and R 4 is Cl.

3. The compound of claim 1 , wherein R 11 , R 12 , R 13 , and R 14 are each Cl.

4. The compound of claim 1 , wherein the compound is

5. The compound of claim 1 , wherein the compound is

6. The compound of claim 1 , wherein the compound is:

7. A compound of the following structure:

or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R 1 , R 2 , R 3 , R 4 , R 11 , R 12 , R 13 , R 14 , and R 15 are each independently selected from hydrogen, halogen, hydroxyl, cyano, nitro, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heteroalkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkoxyl, substituted or unsubstituted aryloxyl, and substituted or unsubstituted carboxyl;
R 5 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a monovalent cation; and
X is hydroxyl, substituted or unsubstituted alkoxyl, or substituted or unsubstituted amino,
wherein if R 1 , R 2 , R 3 , R 4 , R 5 , and R 15 are H and R 11 , R 12 , R 13 , and R 14 , are Cl, then X is other than OEt.

8. A composition, comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

9. A method of treating or preventing cancer in a subject, comprising administering to the subject an effective amount of a compound claim 1 .

10. A method of treating or preventing cancer in a subject, comprising administering to the subject an effective amount of a compound selected from the group consisting of:

11. The method of claim 9 , wherein the cancer is selected from the group consisting of bladder cancer, brain cancer, breast cancer, colorectal cancer, cervical cancer, gastrointestinal cancer, genitourinary cancer, head and neck cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, skin cancer, and testicular cancer.

12. The method of claim 9 , further comprising administering a second compound or composition, wherein the second compound or composition includes an anticancer agent.

13. The method of claim 9 , further comprising administering an effective amount of ionizing radiation to the subject.

14. A method of killing a tumor cell in a subject, comprising:
contacting the tumor cell with an effective amount of a compound claim 1 .

15. A method of killing a tumor cell in a subject, comprising:
contacting the tumor cell with an effective amount of a compound selected from the group consisting of:

16. The method of claim 14 , further comprising contacting the tumor cell with a second compound or composition, wherein the second compound or composition includes an anticancer agent.

17. The method of claim 14 , wherein the tumor cell is a Mcl-1 dependent cell.

18. The method of claim 14 , further comprising irradiating the tumor cell with an effective amount of ionizing radiation.

19. A method of radiotherapy of a tumor, comprising:
contacting the tumor with an effective amount of a compound or composition of claim 1 ; and
irradiating the tumor with an effective amount of ionizing radiation.

Assignees

• H Lee Moffitt Cancer Ct & Res

Inventors

• Li Rongshi
• Sebti Said M
• Liu Yan

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61N2005/1098

  Enhancing the effect of the particle by an injected agent or implanted device · CPC title

• C07D403/04

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

• C07D207/335

  Radicals substituted by nitrogen atoms not forming part of a nitro radical · CPC title