Texaphyrin-Pt(IV) conjugates and compositions for use in overcoming platinum resistance

Patent metadata

Field	Value
Publication number	US-10406167-B2
Application number	US-201515317560-A
Country	US
Kind code	B2
Filing date	Jun 11, 2015
Priority date	Jun 11, 2014
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

The present disclosure relates platinum(IV) and texaphyrin linked conjugates and compositions comprising a texaphyrin and a platinum(IV) agent. The present disclosure also provides pharmaceutical compositions of the conjugates and compositions. Also, provided herein are methods of using the instant compounds in the treatment of cancer such as a platinum resistant cancer.

First claim

What is claimed is:

1. A compound of the formula (VIII):

wherein:
R 1 and R 2 are each

 wherein n is 3 and R 3 is hydrogen or methyl;
X 1 , X 3 , X 4 , and X 6 are each independently selected from alkyl (C≤12) or substituted alkyl (C≤12) ,
X 2 is

wherein:
L 3 , L 4 , and L 6 are each independently selected from ammonia, halide, or L 3 and L 6 are taken together and are alkyldicarboxylate (C≤18) ;
L 5 is aqua, ammonia, halide, hydroxide, alkylcarboxylate (C≤12) , or substituted alkylcarboxylate (C≤12) ;
L 7 is amino, or L 4 and L 7 are taken together and are diaminocycloalkane (C≤12) ;

X 5 are each independently selected from hydroxy or

wherein: L 3 -L 7 are as defined above;

M is a gadolinium(III) ion; and
L 1 and L 2 are each anionic ligands independently selected from fluoride, chloride, bromide, carbonate, hydroxide, perchlorate, nitrate, sulfate, trifluoromethylsulfonate, acetylacetonate, acetate, or trifluoroacetate;

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

2. The compound of claim 1 further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

3. A pharmaceutical composition comprising:
(A) a pharmaceutically acceptable carrier; and
(B) a compound of claim 1 .

4. A method of treating a cancer selected from ovarian cancer, lung cancer, breast cancer, endometrial cancer, brain cancer, skin cancer, head and neck cancer, and colorectal cancer in a patient, comprising administering to the patient in need thereof a therapeutically effective amount of a compound of claim 1 .

5. The method of claim 4 , wherein the cancer is resistant to a platinum chemotherapeutic.

6. The compound of claim 2 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

7. The compound of claim 1 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

8. The compound of claim 7 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

9. The compound of claim 7 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

10. The compound of claim 7 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

11. The pharmaceutical composition of claim 3 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

12. The method of claim 4 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

13. The pharmaceutical composition of claim 3 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

14. The method of claim 4 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

15. The pharmaceutical composition of claim 3 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

16. The method of claim 4 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

17. The pharmaceutical composition of claim 3 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

18. The method of claim 4 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

19. The method of claim 4 , wherein the cancer is ovarian cancer.

20. The compound of claim 1 , further defined as:

or a pharmaceutically acceptable salt, organometallic isomer, or tautomer thereof.

Assignees

• Univ Texas

Inventors

• Sessler Jonathan L
• Arambula Jonathan
• Siddik Zahid H
• Thiabaud Gregory

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K49/106

  the complex-forming compound being cyclic, e.g. DOTA · CPC title

• A61K49/10

  Organic compounds · CPC title