3-aryl-4H-chromene-4-ones as antineoplastic agents for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-9718799-B2
Application number	US-201615149940-A
Country	US
Kind code	B2
Filing date	May 9, 2016
Priority date	May 11, 2015
Publication date	Aug 1, 2017
Grant date	Aug 1, 2017

Abstract

Isoflavonoids or pharmaceutically acceptable salts thereof or pharmaceutically acceptable compositions thereof for the treatment of prostate cancer or for the treatment or inhibition of prostate cancer metastasis in a patient in need thereof are disclosed.

First claim

What is claimed is:

1. A compound having formula (I) or pharmaceutically acceptable salt thereof:

wherein Ar is phenyl; n is an integer from 1 to 5; each X is independently a halide, or alkoxy, or more than one X on Ar together form a cyclic ether structure; and wherein the compound is substituted on the C-2 position with H, alkyl, cycloalkyl or alkoxy, substituted on the C-5, C-6, and C-7 positions independently with H, hydroxy (OH), alkyl, cycloalkyl, alkoxy, acetyl, ester, acetoxy, substituted on the C-8 position with hydroxy (OH), cycloalkyl, alkoxy, acetyl, ester, acetoxy, CH 2 OY 1 where Y 1 is hydrogen, alkyl, acetyl or the substituents on either C-6 and C-7 or the substituents on C-7 and C-8 together form a substituted or unsubstituted, saturated or unsaturated, cyclic or polycyclic ring structure which includes at least one chalcogen, wherein the alkyl, cycloalkyl, and alkoxy substituents can be substituted with one or more of a hydroxy, ester, acetoxy, alkoxy, or carbonyl.

2. The compound of claim 1 , wherein the substituents on C-6 and C-7 or the substituents on C-7 and C-8 together form a substituted or unsubstituted, saturated or unsaturated, cyclic or polycyclic ring structure which includes at least one oxygen.

3. A compound having formula (I) or a pharmaceutically acceptable salt thereof:

wherein Ar is diazinyl, pyrimidinyl, oxazolyl or imidazolyl; n is an integer from 1 to 5; each X is independently a halide, or alkoxy, or more than one X on Ar together form a cyclic ether structure; and wherein the compound is substituted on the C-2 position with H, alkyl, cycloalkyl or alkoxy, substituted on the C-5, C-6, C-7, and C-8 positions independently with H, hydroxy (OH), alkyl, cycloalkyl, alkoxy, acetyl, ester, acetoxy, or the substituents on either C-6 and C-7 or the substituents on C-7 and C-8 together form a substituted or unsubstituted, saturated or unsaturated, cyclic or polycyclic ring structure which includes at least one chalcogen.

4. The compound of claim 1 wherein the C-7 substituent is hydroxy (OH), alkyl, cycloalkyl, alkoxy, acetyl, ester, or acetoxy, and the C-8 substituent is alkoxy, acetyl, ester, acetoxy, or CH 2 OY 1 .

5. The compound of claim 1 , wherein the C-2 substituent is hydrogen H or methyl; Ar includes one or two X groups on the aryl that can be halogens or alkoxy groups or together form a ring structure; the C-5 substituent is H, hydroxy or alkoxy; the C-6 substitutent is hydrogen H; the C-7 substituent is hydroxy or alkoxy; or either C-6 and C-7 together or C-7 and C-8 together form a ring structure including an oxygen.

6. A pharmaceutically acceptable composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable additive.

7. A method of treating prostate cancer, the method comprising administering to a patient in need of such treatment an effective amount of a compound of claim 1 or pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof.

8. A pharmaceutically acceptable composition comprising a compound of claim 3 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable additive.

9. The compound of claim 1 , wherein the C-7 substituent is hydroxy (OH), alkoxy, acetyl, or acetoxy, and the C-8 substituent is CH 2 OY 1 .

10. The compound of claim 1 , wherein the substituents on C-6 and C-7 together form a substituted or unsubstituted, saturated or unsaturated, cyclic or polycyclic ring structure which includes at least one oxygen.

11. The compound of claim 1 , wherein the substituents on C-7 and C-8 together form a substituted or unsubstituted, saturated or unsaturated, cyclic or polycyclic ring structure which includes at least one oxygen.

12. The compound of claim 1 , having one of the following formula or a pharmaceutically acceptable salt thereof:

wherein each of X 2 and X 3 is independently a halide, or alkoxy, or X 2 and X 3 together form a cyclic ether structure.

13. A compound having one of the following formula or a pharmaceutically acceptable salt thereof:

wherein each of X 2 and X 3 is independently a halide, or alkoxy, or X 2 and X 3 together form a cyclic ether structure.

Assignees

• The Univ Of Kentucky Res Found
• Univ Kentucky Res Found

Inventors

• Bondarenko Svitlana P
• Frasinyuk Mykhaylo S
• Liu Chunming
• Watt David S

Classifications

• C07D493/14

  Ortho-condensed systems · CPC title

• C07D493/04

  Ortho-condensed systems · CPC title

• C07D311/36 Primary

  not hydrogenated in the hetero ring, e.g. isoflavones · CPC title

• C07D405/04

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

• C07D311/30 Primary

  not hydrogenated in the hetero ring, e.g. flavones · CPC title