Halogenated diarylacetylenes and methods of treating cancer

Patent metadata

Field	Value
Publication number	US-9895324-B2
Application number	US-201514668865-A
Country	US
Kind code	B2
Filing date	Mar 25, 2015
Priority date	Mar 26, 2014
Publication date	Feb 20, 2018
Grant date	Feb 20, 2018

Abstract

Halogenated diarylacetylenes, e.g., diarylacetylenes having at least one halo substituent in one aryl ring and an amine in the opposing aryl ring, can inhibit the proliferation of LS174T colon cancer cells through the inhibition of c-myc and induction of the cyclin-dependent kinase inhibitor-1 (i.e., p21(Wif1/Cip1)). Such compounds are useful as antineoplastic agents.

First claim

What is claimed is:

1. A method of treating colorectal cancer, the method comprising administering to a patient in need of such treatment an effective amount of a compound according to the following formula:

or a pharmaceutically acceptable salt thereof, wherein each of X 1 through X 5 independently represents H, a lower alkyl, or halo, provided that at least one of X 1 through X 5 is a halo; and each of Y 1 through Y 5 independently represents H, a lower alkyl, or NR 1 R 2 , provided that at least one of Y 1 through Y 5 is NR 1 R 2 , wherein each of R 1 and R 2 independently represents H, or a lower alkyl, provided that at least one of R 1 or R 2 is a lower alkyl.

2. The method of claim 1 , wherein at least two of X 1 through X 5 are halo groups.

3. The method of claim 2 , wherein X 1 through X 5 are either (i) a fluoro and chloro, (ii) both fluoro, or (iii) both chloro groups.

4. The method of claim 1 , wherein both R 1 and R 2 are lower alkyl groups.

5. The method of claim 4 , wherein either X 1 or X 5 or both X 1 and X 5 are halo groups and X 2 through X 4 are H or a lower alkyl.

6. The method of claim 1 , wherein X 1 and/or X 5 are halo groups, X 2 through X 4 are H or a lower alkyl, Y 3 is NR 1 R 2 , and Y 1 , Y 2 , Y 4 , and Y 5 independently represent H or a lower alkyl.

7. The method of claim 1 , wherein X 1 and/or X 5 are fluoro and/or chloro and at least one of R 1 or R 2 is a lower alkyl.

8. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to the following formula:

or a pharmaceutically acceptable salt thereof, wherein each of X 1 through X 5 independently represents H, a lower alkyl, a fluoro or a chloro, provided that at least one of X 1 through X 5 is a fluoro or chloro; and each of Y 1 through Y 5 independently represents H, a lower alkyl, or NR 1 R 2 , provided that at least one of Y 1 through Y 5 is NR 1 R 2 , wherein each of R 1 and R 2 independently represents H, or a lower alkyl, provided that at least one of R 1 or R 2 is a lower alkyl; and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is acceptable to be administered to a mammal.

9. The pharmaceutical composition of claim 8 , wherein at least two of X 1 through X 5 are fluoro, or chloro groups and the remaining X 1 through X 5 are H.

10. The pharmaceutical composition of claim 8 , wherein X 1 and X 5 are either (i) a fluoro and chloro, (ii) both fluoro, (iii) both chloro groups.

11. The pharmaceutical composition of claim 8 , wherein at least one of R 1 , or R 2 , is a lower alkyl.

12. The pharmaceutical composition of claim 11 , wherein the lower alkyl is methyl or ethyl.

Assignees

• Univ Kentucky Res Found

Inventors

• Sviripa Vitaliy M
• Zhang Wen
• Liu Chunming
• Watt David

Classifications

• A61K31/136 Primary

  having the amino group directly attached to the aromatic ring, e.g. benzeneamine · CPC title

• A61P35/00

  Antineoplastic agents · CPC title