Method of making and administering quinoline derivatives as anti-cancer agents

Patent metadata

Field	Value
Publication number	US-9321730-B2
Application number	US-89218807-A
Country	US
Kind code	B2
Filing date	Aug 21, 2007
Priority date	Aug 21, 2007
Publication date	Apr 26, 2016
Grant date	Apr 26, 2016

Abstract

The present invention relates methods of preparing quinoline derivative compounds, and administering such compounds in the treatment of solid and non-solid tumors, notably on liver cancer.

First claim

The invention claimed is:

1. A method of treating cancer in a mammal, the method comprising administering to the mammal an effective amount of a pharmaceutical composition comprising:
(i) a quinoline derivative compound, and
(ii) a pharmaceutically acceptable carrier,
wherein the quinoline derivative compound is selected from the group consisting of 2-ethyl-quinoline, 2-propyl-quinoline, 2-butyl-quinoline, 2-(3-butenyl)-quinoline, 2-pentyl-quinoline, 2-phenethyl-quinoline, 2-methyl-1-(quinolin-2-yl)-propanol, 1,1-diphenyl-2-(quinolin-2-yl)-ethenol, 1-(quinolin-2-ylmethyl)-cyclohexanol, acetic acid quinolin-2-ylmethyl ether, 8-hydroxy-2-quinoline carboxaldehyde, 2-methyl-1,2,3,4-tetrahydroquinoline, 2-ethyl-1,2,3,4-tetrahydroquinoline, 2-propyl-1,2,3,4-tetrahydroquinoline, 2-butyl-1,2,3,4-tetrahydroquinoline, 2,6-dimethyl-1,2,3,4-tetrahydroquinoline, 6-methoxy-2-methyl-1,2,3,4-tetrahydroquinoline, 2-phenethyl-1,2,3,4-tetrahydroquinoline, 1-(1,2,3,4-tetrahydroquinolin-2-ylmethyl)-cyclohexanol, 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline, and 2-methyl-1-(1,2,3,4-tetrahydroquinolin-2-yl)-propan-2-ol; and
wherein the cancer is selected from the group consisting of breast carcinoma, hepatocellular carcinoma, and chronic myelogenous leukemia.

2. The method according to claim 1 , wherein the cancer is breast carcinoma.

3. The method according to claim 1 , wherein the pharmaceutical composition is administered in an amount of from 8 mg/kg/day to about 12 mg/kg/day body weight of the mammal.

4. The method to claim 3 , wherein the pharmaceutical composition is administered over a continuous period of between 5 to 10 days.

5. The method according to claim 1 , wherein the cancer is hepatocellular carcinoma.

6. The method according to claim 1 , wherein the quinoline derivative compound is selected from the group consisting of 8-hydroxy-2-quinoline carbaldehyde, 8-(benzyloxy)-2-methylquinoline, 8-quinolinethiol hydrochloride, and a chiral or a non-chiral tetrahydroquinoline derivative thereof.

7. The method according to claim 6 , wherein the chiral or non-chiral tetrahydroquinoline derivative is 1,2,3,4,-tetrahydro-2-methylquinolin-8-ol or 8-(benzyloxy)-1,2,3,4,-tetrahydro-2-methylquinoline.

8. The method according to claim 1 , wherein the pharmaceutically acceptable carrier is polyethylene glycol, CMC, or a permanently bonded carrier agent.

9. The method according to claim 1 , wherein the pharmaceutically acceptable carrier comprises distilled water, deionized water, glucose, dimethyl sulfoxide or saline water.

10. The method according to claim 1 , wherein the mammal is a human.

11. The method according to claim 1 , wherein the step of administering comprises intratumorally injection, intravenous injection, oral administration, application via mucous membrane, inhalation, or ingestion.

12. The method according to claim 1 , wherein the cancer is chronic myelogenous leukemia.

13. A method of treating cancer in a mammal, the method comprising administering to the mammal an effective amount of a pharmaceutical composition comprising:
(i) a quinoline derivative compound, and
(ii) a pharmaceutically acceptable carrier,
wherein the quinoline derivative compound is selected from the group consisting of 8-hydroxy-2-quinoline carboxaldehyde, 8-hydroxy-2-methylquinoline, 8-methoxy-2-methylquinoline, 8-hydroxy-2-quinoline carbonitrile, 8-hydroxyquinoline, 8-ethoxy-2-methylquinoline, 8-(2-(piperidin-1-yl)ethoxy)-2-methylquinoline, 8-hydroxy-2-quinoline carbaldehyde, 8-(benzyloxy)-2-methylquinoline, 8-quinolinethiol hydrochloride, and 6-methoxy-2-methyl-1,2,3,4-tetrahydroquinoline; and
wherein the cancer is selected from the group consisting of breast carcinoma, hepatocellular carcinoma, and chronic myelogenous leukemia.

14. The method according to claim 13 , wherein the cancer is breast carcinoma.

15. The method according to claim 13 , wherein the pharmaceutical composition is administered in an amount of from 8 mg/kg/day to about 12 mg/kg/day body weight of the mammal.

16. The method according to claim 13 , wherein the pharmaceutical composition is administered over a continuous period of between 5 to 10 days.

17. The method according to claim 13 , wherein the cancer is hepatocellular carcinoma or chronic myelogenous leukemia.

18. The method according to claim 13 , wherein the pharmaceutically acceptable carrier is polyethylene glycol, CMC, or a permanently bonded carrier agent.

19. The method according to claim 13 , wherein the pharmaceutically acceptable carrier comprises distilled water, deionized water, glucose, dimethyl sulfoxide or saline water.

20. The method according to claim 13 , wherein the mammal is a human.

Assignees

• Chan Albert Sun-Chi
• Tang Johnny Cheuk-On
• Lam Kim-Hung
• Chui Chung-Hin
• Kok Stanton Hon-Lung
• Chan Sau Hing
• Cheung Filly
• Gambari Roberto
• Cheng Chor Hing
• Univ Hong Kong Polytechnic

Inventors

• Chan Albert Sun-Chi
• Tang Johnny Cheuk-On
• Lam Kim-Hung
• Chui Chung-Hin
• Kok Stanton Hon-Lung
• Chan Sau Hing
• Cheung Filly
• Gambari Roberto
• Cheng Chor Hing

Classifications

• C07D215/20

  Oxygen atoms · CPC title

• C07D215/14

  Radicals substituted by oxygen atoms · CPC title

• C07D215/06 Primary

  having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom · CPC title

• A61K31/47

  Quinolines; Isoquinolines · CPC title

• C07D215/26

  Alcohols; Ethers thereof · CPC title