Macrocyclic compound and uses thereof

Patent metadata

Field	Value
Publication number	US-9938288-B1
Application number	US-201715814105-A
Country	US
Kind code	B1
Filing date	Nov 15, 2017
Priority date	Apr 5, 2017
Publication date	Apr 10, 2018
Grant date	Apr 10, 2018

Abstract

The present invention provides novel Compound (1) having tumor vascular remodeling effect and/or anti-CAF (Cancer Associated Fibroblasts) activity, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, and a medical uses thereof.

First claim

What is claimed is:

1. A compound of the following structure:

or a pharmaceutically acceptable salt thereof.

2. The compound or pharmaceutically acceptable salt thereof according to claim 1 for use in inhibiting growth of tumor or cancer characterized by angiogenesis, invasion, or metastasis.

3. The compound or pharmaceutically acceptable salt thereof according to claim 1 for use in the treatment of tumor or cancer characterized by angiogenesis, invasion, or metastasis.

4. A pharmaceutical composition comprising the compound of claim 1 , or pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier.

5. A method for treating a tumor or cancer characterized by angiogenesis, invasion or metastasis in a subject comprising administering to the subject the compound of claim 1 , or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.

6. The method of claim 5 , wherein the cancer or tumor is head and neck cancer, breast cancer, esophageal cancer, uterine cancer, ovarian cancer, colorectal cancer, endometrial cancer, or a sarcoma.

7. The method of claim 6 , wherein the cancer or tumor is head and neck cancer.

8. The method of claim 7 , wherein the cancer or tumor is squamous cell carcinoma of the head and neck (SCCHN).

9. The method of claim 6 , wherein the cancer or tumor is breast cancer.

10. The method of claim 9 , wherein the cancer or tumor is HER2-positive breast cancer.

11. The method of claim 9 , wherein the cancer or tumor is HER2-negative breast cancer.

12. The method of claim 9 , wherein the cancer or tumor is triple negative breast cancer.

13. The method of claim 6 , wherein the cancer or tumor is colorectal cancer.

14. The method of claim 6 , wherein the cancer or tumor is esophageal cancer.

15. The method of claim 14 , wherein the cancer or tumor is esophageal adenocarcinoma.

16. The method of claim 6 , wherein the cancer or tumor is uterine cancer.

17. The method of claim 6 , wherein the cancer or tumor is ovarian cancer.

18. The method of claim 6 , wherein the cancer or tumor is a sarcoma.

19. The method of claim 18 , wherein the cancer or tumor is uterine sarcoma, fibrosarcoma, or angiosarcoma.

20. The method of claim 5 comprising further treating the subject with radiation therapy.

21. The method of claim 5 comprising further treating the subject with a Programmed Death 1 protein (PD-1) antibody.

22. The method of claim 5 comprising further treating the subject with an anti-EGFR (epidermal growth factor receptor) mAb.

23. The method of claim 22 , wherein the cancer or tumor is head and neck cancer.

24. The method of claim 23 , wherein the cancer or tumor is squamous cell carcinoma of the head and neck (SCCHN).

25. The method of claim 22 , wherein the anti-EGFR (epidermal growth factor receptor) mAb is cetuximab.

26. The method of claim 5 comprising further treating the subject with an HER2 (human epidermal growth factor receptor) mAb.

27. The method of claim 26 , wherein the cancer is breast cancer.

28. The method of according to claim 26 , wherein the HER2 (human epidermal growth factor receptor) mAb is trastuzumab.

29. A method for treating HER2-negative breast cancer or squamous cell carcinoma of the head and neck (SCCHN) in a subject comprising administering to the subject the compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignees

• Harvard College
• Eisai R&D Man Co Ltd

Inventors

• Kishi Yoshito
• Kira Kazunobu
• Ito Ken

Classifications

• C07K16/2818

  against CD28 or CD152 · CPC title

• C07K16/2863

  against receptors for growth factors, growth regulators · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07D493/22 Primary

  in which the condensed system contains four or more hetero rings · CPC title