Compounds and methods for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-10166229-B2
Application number	US-201615385040-A
Country	US
Kind code	B2
Filing date	Dec 20, 2016
Priority date	May 26, 2005
Publication date	Jan 1, 2019
Grant date	Jan 1, 2019

Abstract

Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed in connection with modification of procaspases such as procaspase-3. In embodiments, compositions are capable of activation of procaspase-3.

First claim

What is claimed is:

1. A method for treating cancer comprising administering to a patient having cancer a therapeutically effective amount of a compound of formula ZZ:

wherein
each R is independently hydrogen, halogen, allyl, or short alkyl;
n is 1 or 2;
R 2 is hydrogen or short alkyl;
R 3 is hydrogen, halogen, alkyl, haloalkyl, allyl, alkenyl, alkenol, alkanol, or haloalkenyl;
R 4 and R 5 are N; or R 4 is N and R 5 is C; or R 4 and R 5 is C; and
A is oxygen or sulfur;

or a salt thereof;
wherein the cancer is thereby treated.

2. The method of claim 1 wherein the cancer is adrenal cancer, brain cancer, breast cancer, colon cancer, leukemia, liver cancer, lung cancer, lymphoma, melanoma, neuroblastoma, or renal cancer.

3. The method of claim 2 wherein R 2 is hydrogen.

4. The method of claim 3 wherein R 3 is allyl.

5. The method of claim 3 wherein R 3 is hydrogen.

6. The method of claim 3 wherein R 4 and R 5 are N.

7. The method of claim 3 wherein n is 1.

8. The method of claim 3 wherein A is oxygen.

9. The method of claim 3 wherein each R is hydrogen.

10. The method of claim 3 wherein at least one R is halogen.

11. The method of claim 3 wherein at least one R is allyl.

12. The method of claim 3 wherein at least one R is short alkyl.

13. The method of claim 3 wherein the compound of formula ZZ is:

or a salt thereof.

14. The method of claim 13 wherein the compound of formula ZZ is:

15. A method for treating cancer comprising administering to a patient having cancer a therapeutically effective amount of a compound of formula Z2:

wherein
R 1 and R 2 independently represent substitution on the indicated rings with one or more hydrogen, halogen, alkyl, allyl, haloalkyl, alkenyl, alkenol, alkanol, or haloalkenyl;
or a salt thereof;

wherein the cancer is adrenal cancer, brain cancer, breast cancer, colon cancer, leukemia, liver cancer, lung cancer, lymphoma, melanoma, neuroblastoma, or renal cancer, and the cancer is thereby treated.

16. The method of claim 15 wherein the compound of formula Z2 is:

17. A method for treating cancer comprising administering to a patient having cancer a therapeutically effective amount of the compound:

or a salt thereof;
wherein the cancer is thereby treated.

18. The method of claim 17 wherein the cancer is adrenal, brain cancer, breast cancer, colon cancer, leukemia, liver cancer, lung cancer, lymphoma, melanoma, neuroblastoma, or renal cancer.

19. The method of claim 18 wherein the cancer is breast cancer, colon cancer, lung cancer or leukemia.

20. The method of claim 18 wherein the compound is

or a salt thereof.

21. The method of claim 3 wherein the compound of formula ZZ is:

or a salt thereof.

22. A method for treating cancer comprising administering to a patient having cancer a therapeutically effective amount of the compound:

or a salt thereof;
wherein the cancer is thereby treated.

23. The method of claim 18 wherein the compound is

or a salt thereof.

Assignees

• Univ Illinois

Inventors

• Hergenrother Paul J
• Putt Karson S
• Peterson Quinn P
• Fako Valerie

Classifications

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/495 Primary

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• A61K31/445

  Non condensed piperidines, e.g. piperocaine · CPC title

• A61K31/45

  having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide · CPC title

• C07D295/15

  to an acyclic saturated chain · CPC title