Macrocyclic compound and uses thereof

Patent metadata

Field	Value
Publication number	US-2023406863-A1
Application number	US-202318339227-A
Country	US
Kind code	A1
Filing date	Jun 21, 2023
Priority date	Apr 5, 2017
Publication date	Dec 21, 2023
Grant date	—

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 medical uses thereof.

First claim

What is claimed is:

1 . A compound of the following structure:

or a pharmaceutically acceptable salt thereof.

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

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

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

5 . The compound for use of claim 3 or 4 , wherein the cancer or tumor is head and neck cancer, breast cancer, esophageal cancer, uterine cancer, ovarian cancer, colorectal cancer, endometrial cancer, gastric cancer, small bowel cancer, bladder cancer, or a sarcoma.

6 . The compound for use of claim 5 , wherein the cancer or tumor is head and neck cancer.

7 . The compound for use of claim 6 , wherein the cancer or tumor is squamous cell carcinoma of the head and neck (SCCHN).

8 . The compound for use of claim 6 , wherein the cancer is adenoid cystic carcinoma.

9 . The compound for use of claim 5 , wherein the cancer or tumor is breast cancer.

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

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

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

13 . The compound for use of claim 5 , wherein the cancer or tumor is colorectal cancer.

14 . The compound for use of claim 5 , wherein the cancer or tumor is esophageal cancer.

15 . The compound for use of claim 14 , wherein the cancer or tumor is esophageal adenocarcinoma.

16 . The compound for use of claim 5 , wherein the cancer or tumor is uterine cancer.

17 . The compound for use of claim 5 , wherein the cancer or tumor is ovarian cancer.

18 . The compound for use of claim 5 , wherein the cancer or tumor is a sarcoma.

19 . The compound for use of claim 18 , wherein the cancer or tumor is uterine sarcoma, fibrosarcoma, synovial sarcoma, soft tissue sarcoma, or angiosarcoma.

20 . The compound for use of claim 5 , wherein the cancer or tumor is gastric cancer.

21 . The compound for use of claim 5 , wherein the cancer or tumor is small bowel cancer.

22 . The compound for use of claim 21 , wherein the cancer or tumor is small bowel adenocarcinoma.

23 . The compound for use of claim 5 , wherein the cancer or tumor is bladder cancer.

24 . The compound for use of claim 5 , wherein the cancer or tumor is urothelial cancer.

25 . The compound for use of any one of claims 4 - 24 , for use in combination with a Programmed Death 1 protein (PD-1) antibody.

26 . The compound for use of any one of claims 4 - 24 , for use in combination with a Programmed Death L1 protein (PD-L1) antibody.

27 . The compound for use of any one of claims 4 - 24 , for use in combination with an anti-EGFR (epidermal growth factor receptor) antibody.

28 . The compound for use of claim 27 , wherein the anti-EGFR antibody is an anti-EGFR mAb.

29 . The compound for use of claim 27 or 28 , wherein the cancer or tumor is head and neck cancer.

30 . The compound for use of claim 29 , wherein the cancer or tumor is squamous cell carcinoma of the head and neck (SCCHN).

31 . The compound for use of any one of claims 28 - 30 , wherein the anti-EGFR mAb is cetuximab.

32 . The compound for use of any one of claims 4 - 24 , for use in combination with an HER2 (human epidermal growth factor receptor) antibody.

33 . The compound for use of claim 32 , wherein the HER2 antibody is an HER2 mAb.

34 . The compound for use of claim 32 or 33 , wherein the cancer is breast cancer.

35 . The compound for use of claim 33 or 34 , wherein the HER2 mAb is trastuzumab.

36 . The compound for use of any one of claims 4 - 24 , for use in combination with radiation therapy.

37 . The compound for use of any one of claims 4 - 24 , for use in combination with surgery.

38 . 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.

39 . The method of claim 38 , wherein the cancer or tumor is head and neck cancer, breast cancer, esophageal cancer, uterine cancer, ovarian cancer, colorectal cancer, endometrial cancer, gastric cancer, small bowel cancer, bladder cancer, or a sarcoma.

40 . The method of claim 39 , wherein the cancer or tumor is head and neck cancer.

41 . The method of claim 40 , wherein the cancer or tumor is squamous cell carcinoma of the head and neck (SCCHN).

42 . The method of claim 40 , wherein the cancer is adenoid cystic carcinoma.

43 . The method of claim 39 , wherein the cancer or tumor is breast cancer.

44 . The method of claim 43 , wherein the cancer or tumor is HER2-positive breast cancer.

45 . The method of claim 43 , wherein the cancer or tumor is HER2-negative breast cancer.

46 . The method of claim 43 , wherein the cancer or tumor is triple negative breast cancer.

47 . The method of claim 39 , wherein the cancer or tumor is colorectal cancer.

48 . The method of claim 39 , wherein the cancer or tumor is esophageal cancer.

49 . The method of claim 48 , wherein the cancer or tumor is esophageal adenocarcinoma.

50 . The method of claim 39 , wherein the cancer or tumor is uterine cancer.

51 . The method of claim 39 , wherein the cancer or tumor is ovarian cancer.

52 . The method of claim 39 , wherein the cancer or tumor is a sarcoma.

53 . The method of claim 52 , wherein the cancer or tumor is uterine sarcoma, fibrosarcoma, synovial sarcoma, soft tissue sarcoma, or angiosarcoma.

54 . The method of claim 39 , wherein the cancer or tumor is gastric cancer.

55 . The method of claim 39 , wherein the cancer or tumor is small bowel cancer.

56 . The method of claim 55 , wherein the cancer or tumor is small bowel adenocarcinoma.

57 . The method of claim 39 , wherein the cancer or tumor is bladder cancer.

58 . The method of claim 39 , wherein the cancer or tumor is urothelial cancer.

59 . The method of any one of claims 39 - 58 comprising further treating the subject with a Programmed Death 1 protein (PD-1) antibody.

60 . The method of any one of claims 39 - 58 comprisi

Assignees

• Harvard College
• Eisai R&D Man Co Ltd

Inventors

• Kishi Yoshito
• Kira Kazunobu
• Ito Ken

Classifications

• C07D493/22 Primary

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/357

  having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• C07K16/2818

  against CD28 or CD152 · CPC title