Procaspase activating compounds

Patent metadata

Field	Value
Publication number	US-9643960-B2
Application number	US-201514822830-A
Country	US
Kind code	B2
Filing date	Aug 10, 2015
Priority date	Feb 9, 2009
Publication date	May 9, 2017
Grant date	May 9, 2017

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 that have lower neurotoxicity effects than other compounds.

First claim

What is claimed is:

1. A therapeutic composition comprising a compound of Formula (FX2):

wherein
one of R 10 , R 11 , R 12 , R 13 or R 14 contains a polar group selected from the group consisting of: a sulfonamide group, a nitro group, an amino group, a carboxy group, and an aryl sulfonyl group;
the others of R 10 , R 11 , R 12 , R 13 and R 14 , and R 3 , R 7 , R 8 , or R 9 are each independently selected from the group consisting of: hydrogen, halogen, a hydroxyl group, C1-C6 alkyl, C1-C6 alkoxy, and C2-C6 alkenyl; and
R 2 is hydrogen or C1-C6 alkyl;
or a salt thereof;

in combination with a pharmaceutically acceptable carrier or excipient.

2. The composition of claim 1 wherein one of R 10 , R 11 , R 12 , R 13 , or R 14 of compound of Formula (FX2) is:

where R a and R b are each independently hydrogen or C1-C6 alkyl.

3. The composition of claim 2 wherein R 12 is —S(O) 2 NH 2 .

4. The composition of claim 3 wherein R 3 is allyl and R 2 is hydrogen.

5. The composition of claim 1 wherein the composition is a composition formulated for enteral, parenteral, topical, aerosol, or inhalation administration.

6. The composition of claim 1 wherein the composition is an aqueous solution formulated for intravenous or intraperitoneal administration.

7. The composition of claim 1 wherein the composition is a solid, gel, or liquid formulated for oral administration.

8. A compound of Formula (FX2):

wherein
at least one of R 10 , R 11 , R 12 , R 13 , R 14 , R 3 , R 7 , R 8 , or R 9 is a sulfonyl group, a methoxy group, or a fluorescent label moiety;
the others of R 10 , R 11 , R 12 , R 13 , R 14 , R 3 , R 7 , R 8 , or R 9 are each independently selected from the group consisting of: hydrogen, a hydroxyl group, C1-C6 alkyl, C1-C6 alkoxy, and C2-C6 alkenyl, provided that when R 3 is allyl, R 12 is not methoxy, and R 10 and R 13 are not both methoxy, and provided that when R 3 is H, R 10 and R 13 are not both methoxy;
R 6 is hydrogen or C1-C6 alkyl; and
R 2 is hydrogen or C1-C6 alkyl;

or a salt thereof.

9. The compound of claim 8 wherein R 2 is hydrogen and R 3 is hydrogen, allyl, or methoxy.

10. The compound of claim 9 wherein R 10 is —CH 2 S(O) 2 Ph.

11. The compound of claim 9 wherein R 12 is —OMe.

12. The compound of claim 8 wherein R 3 is hydrogen, allyl, or —OMe, and R 2 is hydrogen, each of R 7 , R 8 and R 9 is hydrogen, and either R 10 is —CH 2 S(O) 2 Ph or R 12 is —OMe.

13. The compound of claim 8 wherein the compound is FX7:

14. The compound of claim 8 wherein the compound is:

15. The compound of claim 8 wherein the compound is FX9:

16. The compound of claim 8 wherein the compound is:

17. A composition comprising a compound of claim 8 in combination with a pharmaceutically acceptable carrier or excipient.

18. The composition of claim 17 wherein the composition is a composition formulated for enteral, parenteral, topical, aerosol, or inhalation administration.

19. The composition of claim 17 wherein the composition is an aqueous solution formulated for intravenous or intraperitoneal administration.

20. The composition of claim 17 wherein the composition is a solid, gel, or liquid formulated for oral administration.

21. A compound of Formula (FX2):

wherein
R 2 is hydrogen;
R 3 is hydrogen, allyl, or methoxy;
R 10 is —CH 2 S(O) 2 Ph;
R 7 , R 8 , R 9 , R 11 , R 12 , R 13 , and R 14 are each independently selected from the group consisting of: hydrogen, halogen, a hydroxyl group, C1-C6 alkyl, C1-C6 alkoxy, and C2-C6 alkenyl; and
R 6 is hydrogen or C1-C6 alkyl;

or a salt thereof.

Assignees

• Univ Illinois

Inventors

• Hergenrother Paul J
• Peterson Quinn Patrick
• Hsu Danny Chung
• West Diana C
• Fan Timothy M
• Novotny Chris J

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61P35/02

  specific for leukemia · CPC title

• A61K31/445

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

• C07D295/15 Primary

  to an acyclic saturated chain · CPC title