USE OF BENZO-HETEROCYCLE DERIVATIVES FOR PREVENTING AND TREATING CANCER OR FOR INHIBITING CANCER METASTASIS

• US 20120283300A1
• Filed: 05/07/2012
• Published: 11/08/2012
• Est. Priority Date: 11/05/2009
• Status: Active Grant

• Current Assignee: Medicinal Bio-convergence Research Center
• Original Assignee: Seoul National University R&DB Foundation (Seoul National University)
• Inventors: Kim, Sunghoon, Choi, Jin Woo, Lee, Jin Young, Han, Gyoon Hee, Yang, Jee Sun, Lee, Chul Ho, Kim, Dae Gyu
• Granted Patent: US 10,130,611 B2
• Time in Patent Office: Days
• US Class Current: 514/367
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/423 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 7/06 Antianaemics

Abstract

This application relates to a novel benzo-heterocycle derivative and more particularly, it relates a composition for preventing and treating cancer or for inhibiting metastasis comprising benzo-heterocycle derivative or pharmaceutically acceptable salts thereof as an active ingredient. The present inventors confirmed that KRS has an effect on cancer metastasis by facilitating cancer (or tumor) cell migration through interaction with 67LR, and also found that a substance inhibiting the interaction between KRS and 67LR can prevent and treat cancer by inhibiting cancer cell metastasis. Accordingly, the composition of the present invention can inhibit cancer metastasis, and thus provide a novel means for prevention and treatment of cancer.

Claims

1. A pharmaceutical composition for preventing and treating cancer comprising a benzo-heterocycle derivative represented by Formula 1 or pharmaceutically acceptable salts thereof as an active ingredient:

2. The pharmaceutical composition for preventing and treating cancer of claim 1, wherein the composition is selected from the group consisting of N-(6-Methoxy-benzooxazol-2-yl)-benzamide of formula 2, N-(5-Methoxy-benzooxazol-2-yl)-benzamide of formula 3, (5-Chloro-benzooxazol-2-yl)-phenyl-amine of formula 4, (5-Chloro-benzooxazol-2-yl)-(4-ethyl-phenyl)-amine) of formula 5, (5-Chloro-benzooxazol-2-yl)-(3,4-dichloro-phenyl)-amine) of formula 6, (5-Nitro-benzooxazol-2-yl)-(4-phenylazo-phenyl)-amine) of formula 7, N-Benzooxazol-2-yl-benzamide of formula 8, N-(5-Nitro-benzooxazol-2-yl)-benzamide of formula 9, N-(5-Methoxy-benzooxazol-2-yl)-benzamide of formula 10, N-(5-Methyl-benzooxazol-2-yl)-benzamide of formula 11, N-(6-Nitro-benzothiazol-2-yl)-4-trifluoromethyl-benzamide of formula 12, [2-(5-Methyl-benzooxazol-2-yl)-phenoxy]-acetic acid of formula 13, (2-(2,4,6-Trimethyl-phenyl)-benzooxazol-5-ylamine of formula 14, 2-[2-(4-Methyl-benzoylimino)-benzothiazol-3-yl]-butyric acid of formula 15, (2-(2,6-Dimethoxy-phenyl)-benzothiazole of formula 16 and (2-Chloro-4-fluoro-benzyl)-(5-fluoro-1H-indol-3-ylmethyl)-amine of formula 17 or pharmaceutically acceptable salts thereof as an active ingredient.

3. The composition of claim 1, wherein the cancer is selected from the group consisting of colon cancer, lung cancer, liver cancer, stomach cancer, esophagus cancer, pancreatic cancer, gall bladder cancer, kidney cancer, prostate cancer, testis cancer, cervical cancer, endometrial carcinoma, choriocarcinoma, ovarian cancer, breast cancer, thyroid cancer, brain tumor, head or neck cancer, malignant melanoma, lymphoma and aplastic anemia.

4. The composition of claim 1, wherein the prevention and treatment of cancer are performed by inhibiting metastasis of cancer cells.

6. The pharmaceutical composition for inhibiting metastasis of claim 1, wherein the composition is selected from the group consisting of N-(6-Methoxy-benzooxazol-2-yl)-benzamide of formula 2, N-(5-Methoxy-benzooxazol-2-yl)-benzamide of formula 3, (5-Chloro-benzooxazol-2-yl)-phenyl-amine of formula 4, (5-Chloro-benzooxazol-2-yl)-(4-ethyl-phenyl)-amine) of formula 5, (5-Chloro-benzooxazol-2-yl)-(3,4-dichloro-phenyl)-amine) of formula 6, (5-Nitro-benzooxazol-2-yl)-(4-phenylazo-phenyl)-amine) of formula 7, N-Benzooxazol-2-yl-benzamide of formula 8, N-(5-Nitro-benzooxazol-2-yl)-benzamide of formula 9, N-(5-Methoxy-benzooxazol-2-yl)-benzamide of formula 10, N-(5-Methyl-benzooxazol-2-yl)-benzamide of formula 11, N-(6-Nitro-benzothiazol-2-yl)-4-trifluoromethyl-benzamide of formula 12, [2-(5-Methyl-benzooxazol-2-yl)-phenoxy]-acetic acid of formula 13, (2-(2,4,6-Trimethyl-phenyl)-benzooxazol-5-ylamine of formula 14, 2-[2-(4-Methyl-benzoylimino)-benzothiazol-3-yl]-butyric acid of formula 15, (2-(2,6-Dimethoxy-phenyl)-benzothiazole of formula 16 and (2-Chloro-4-fluoro-benzyl)-(5-fluoro-1 H-indol-3-ylmethyl)-amine of formula 17 or pharmaceutically acceptable salts thereof as an active ingredient.

5. A pharmaceutical composition for inhibiting cancer metastasis comprising a benzo-heterocycle derivative represented by Formula 1 or pharmaceutically acceptable salts thereof as an active ingredient:

7. Use of benzo-heterocycle derivative represented by formula 1 or pharmaceutically acceptable salts thereof for preparing an agent for preventing and treating cancer:

11. Use of claim 7, wherein benzo-heterocycle derivative represented by formula 1 is selected from the group consisting of N-(6-Methoxy-benzooxazol-2-yl)-benzamide of formula 2, N-(5-Methoxy-benzooxazol-2-yl)-benzamide of formula 3, (5-Chloro-benzooxazol-2-yl)-phenyl-amine of formula 4, (5-Chloro-benzooxazol-2-yl)-(4-ethyl-phenyl)-amine) of formula 5, (5-Chloro-benzooxazol-2-yl)-(3,4-dichloro-phenyl)-amine) of formula 6, (5-Nitro-benzooxazol-2-yl)-(4-phenylazo-phenyl)-amine) of formula 7, N-Benzooxazol-2-yl-benzamide of formula 8, N-(5-Nitro-benzooxazol-2-yl)-benzamide of formula 9, N-(5-Methoxy-benzooxazol-2-yl)-benzamide of formula 10, N-(5-Methyl-benzooxazol-2-yl)-benzamide of formula 11, N-(6-Nitro-benzothiazol-2-yl)-4-trifluoromethyl-benzamide of formula 12, [2-(5-Methyl-benzooxazol-2-yl)-phenoxy]-acetic acid of formula 13, (2-(2,4,6-Trimethyl-phenyl)-benzooxazol-5-ylamine of formula 14, 2-[2-(4-Methyl-benzoylimino)-benzothiazol-3-yl]-butyric acid of formula 15, (2-(2,6-Dimethoxy-phenyl)-benzothiazole of formula 16 and (2-Chloro-4-fluoro-benzyl)-(5-fluoro-1H-indol-3-ylmethyl)-amine of formula 17.

13. The use of claim 7, wherein the cancer is selected from the group consisting of colon cancer, lung cancer, liver cancer, stomach cancer, esophagus cancer, pancreatic cancer, gall bladder cancer, kidney cancer, prostate cancer, testis cancer, cervical cancer, endometrial carcinoma, choriocarcinoma, ovarian cancer, breast cancer, thyroid cancer, brain tumor, head or neck cancer, malignant melanoma, lymphoma and aplastic anemia.

8. Use of benzo-heterocycle derivative represented by formula 1 or pharmaceutically acceptable salts thereof for preparing an agent for inhibiting metastasis:

9. A method for preventing and treating cancer comprising administering to a subject in need thereof an effective amount of benzo-heterocycle derivative represented by formula 1 or pharmaceutically acceptable salts thereof.

12. Use of claim 9, wherein benzo-heterocycle derivative represented by formula 1 is selected from the group consisting of N-(6-Methoxy-benzooxazol-2-yl)-benzamide of formula 2, N-(5-Methoxy-benzooxazol-2-yl)-benzamide of formula 3, (5-Chloro-benzooxazol-2-yl)-phenyl-amine of formula 4, (5-Chloro-benzooxazol-2-yl)-(4-ethyl-phenyl)-amine) of formula 5, (5-Chloro-benzooxazol-2-yl)-(3,4-dichloro-phenyl)-amine) of formula 6, (5-Nitro-benzooxazol-2-yl)-(4-phenylazo-phenyl)-amine) of formula 7, N-Benzooxazol-2-yl-benzamide of formula 8, N-(5-Nitro-benzooxazol-2-yl)-benzamide of formula 9, N-(5-Methoxy-benzooxazol-2-yl)-benzamide of formula 10, N-(5-Methyl-benzooxazol-2-yl)-benzamide of formula 11, N-(6-Nitro-benzothiazol-2-yl)-4-trifluoromethyl-benzamide of formula 12, [2-(5-Methyl-benzooxazol-2-yl)-phenoxy]-acetic acid of formula 13, (2-(2,4,6-Trimethyl-phenyl)-benzooxazol-5-ylamine of formula 14, 2-[2-(4-Methyl-benzoylimino)-benzothiazol-3-yl]-butyric acid of formula 15, (2-(2,6-Dimethoxy-phenyl)-benzothiazole of formula 16 and (2-Chloro-4-fluoro-benzyl)-(5-fluoro-1H-indol-3-ylmethyl)-amine of formula 17.

14. The use of claim 9, wherein the cancer is selected from the group consisting of colon cancer, lung cancer, liver cancer, stomach cancer, esophagus cancer, pancreatic cancer, gall bladder cancer, kidney cancer, prostate cancer, testis cancer, cervical cancer, endometrial carcinoma, choriocarcinoma, ovarian cancer, breast cancer, thyroid cancer, brain tumor, head or neck cancer, malignant melanoma, lymphoma and aplastic anemia.

10. A method for inhibiting metastasis comprising administering to a subject in need thereof an effective amount of benzo-heterocycle derivative represented by formula 1 or pharmaceutically acceptable salts thereof.