Compounds as HIF-1α inhibitors and manufacturing process thereof

Patent metadata

Field	Value
Publication number	US-9789114-B2
Application number	US-201615067057-A
Country	US
Kind code	B2
Filing date	Mar 10, 2016
Priority date	Sep 27, 2011
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

The present invention relates to novel compounds as HIF-1α inhibitors, manufacturing process thereof, and a pharmaceutical compositions. The compounds according to the present invention having inhibition activity against HIF-1α, can be used as a therapeutic prevention and/or treatment for various solid cancers such as colon cancer, liver cancer, stomach cancer and breast cancer. Also, the compounds according to the present invention are useful in the treatment of diabetic retinopathy and rheumatoid arthritis, which are aggravated by HIF-1α-mediated VEGFA expression.

First claim

We claim:

1. A method of treating colon cancer in a subject in need thereof, comprising administering an effective amount of a pharmaceutical composition comprising a compound selected from the group consisting of:
2-(4-(Adamantan-1-yl)phenoxy)-1-(4-methylpiperazin-1-yl)ethanone (“I-3”);
2-(4-(Adamantan-1-yl)-2-methylphenoxy)-1-morpholinoethanone (“I-6”);
3-(4-(Adamantan-1-yl)phenoxy)-1-(4-methylpiperazin-1-yl)propan-1-one (“I-8”);
4-(2-(4-(Adamantan-1-yl)-2-methylphenoxy)acetyl)-1,1-dimethylpiperazin-1-ium iodide (“I-16”);
4-(4-(4-(Adamantan-1-yl)phenoxy)butanoyl)-1,1-dimethylpiperazin-1-ium iodide (“I-22”); and
2-(4-(Adamantan-1-yl)phenoxy)-2-methyl-1-(4-methylpiperazin-1-yl)propan-1-one (“I-23”),

or a pharmaceutically acceptable base or acid addition salt, hydrate, or solvate thereof.

2. The method of claim 1 , wherein the compound is I-3.

3. The method of claim 1 , wherein, the compound suppresses the growth and metastasis of colon cancer.

4. A method of treating rectal cancer in a subject in need thereof, comprising administering an effective amount of a pharmaceutical composition comprising a compound selected from the group consisting of:
2-(4-(Adamantan-1-yl)phenoxy)-1-(4-methylpiperazin-1-yl)ethanone (“I-3”);
2-(4-(Adamantan-1-yl)-2-methylphenoxy)-1-morpholinoethanone (“I-6”);
3-(4-(Adamantan-1-yl)phenoxy)-1-(4-methylpiperazin-1-yl)propan-1-one (“I-8”);
4-(2-(4-(Adamantan-1-yl)-2-methylphenoxy)acetyl)-1,1-dimethylpiperazin-1-ium iodide (“I-16”);
4-(4-(4-(Adamantan-1-yl)phenoxy)butanoyl)-1,1-dimethylpiperazin-1-ium iodide (“I-22”); and
2-(4-(Adamantan-1-yl)phenoxy)-2-methyl-1-(4-methylpiperazin-1-yl)propan-1-one (“I-23”),

or a pharmaceutically acceptable base or acid addition salt, hydrate or solvate thereof.

5. The method of claim 4 , wherein the compound is I-3.

6. A method of treating cancer in a subject in need thereof, comprising administering an effective amount of a pharmaceutical composition comprising I-3, wherein the cancer is selected from the group consisting of pro static cancer, renal cell carcinoma, and pancreatic cancer.

Assignees

• Dongguk Univ Industry-Academic Coop Found
• Korea Res Inst Bioscience & Biotechnology

Inventors

• Lee Kyeong
• Won Mi-Sun
• Kim Hwan-Mook
• Park Song-Kyu
• Lee Ki-Ho
• Lee Chang-Woo
• Kim Bo-Kyung
• Ban Hyun-Seung
• Chung Kyung-Sook
• Ravi Naik

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P27/02

  Ophthalmic agents · CPC title