Amide compound, and Pin1 inhibitor, therapeutic agent for inflammatory diseases and therapeutic agent for cancer that use the same

Patent metadata

Field	Value
Publication number	US-11504379-B2
Application number	US-201816636746-A
Country	US
Kind code	B2
Filing date	Aug 6, 2018
Priority date	Aug 7, 2017
Publication date	Nov 22, 2022
Grant date	Nov 22, 2022

Abstract

The purpose of the invention is to develop, as drug-candidate compounds, a group of novel compounds having the activity of inhibiting functions of Pin1. The invention provides: a compound represented by formula (I) or a salt thereof; and a Pin1 inhibitor, a pharmaceutical composition, a therapeutic or prophylactic agent for inflammatory diseases, a therapeutic or prophylactic agent for cancer, and a therapeutic or prophylactic agent for adiposity that use said compound/salt.

First claim

The invention claimed is:

1. A compound represented by Formula (I), or a salt thereof:

wherein m represents an integer of 0 to 2, and n represents an integer of 0 to 1, provided that 0≤m+n≤2;
R 1 represents a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted amino group;
R 2 represents an optionally substituted fluorenyl group, a substituted naphthyl group, or an optionally substituted group represented by any one of the following structures:

R 3 represents 0 to 7 identical or different substituents attached to the naphthyl group; and
X represents a single bond, —CH 2 — group, or —NH— group.

2. The compound or a salt thereof according to claim 1 , wherein m is 1 and n is 0.

3. The compound or a salt thereof according to claim 1 , wherein R 1 represents a hydrogen atom.

4. The compound or a salt thereof according to claim 1 , wherein X represents a single bond.

5. A Pin1 inhibitor comprising a compound represented by Formula (I) or a salt thereof:

wherein m represents an integer of 0 to 2, and n represents an integer of 0 to 1, provided that 0≤m+n≤2;
R 1 represents a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted amino group;
R 2 represents an optionally substituted fluorenyl group, a substituted naphthyl group, or an optionally substituted group represented by any one of the following structures:

R 3 represents 0 to 7 identical or different substituents attached to the naphthyl group; and
X represents a single bond, —CH 2 — group, or —NH— group.

6. A pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable carrier.

7. A therapeutic agent for the treatment of an inflammatory disease associated with fibrosis, comprising a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient:

wherein m represents an integer of 0 to 2, and n represents an integer of 0 to 1, provided that 0≤m+n≤2;
R 1 represents a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted amino group;
R 2 represents an optionally substituted fluorenyl group, a substituted naphthyl group, or an optionally substituted group represented by any one of the following structures:

R 3 represents 0 to 7 identical or different substituents attached to the naphthyl group; and
X represents a single bond, —CH 2 — group, or —NH— group.

8. The therapeutic agent according to claim 7 , further comprising an active ingredient of at least one additional drug for the treatment of the inflammatory disease associated with fibrosis.

9. A method of treating an inflammatory disease associated with fibrosis, comprising administering the therapeutic agent according to claim 7 , in combination with at least one additional drug for the treatment of the inflammatory disease associated with fibrosis.

10. A method of preparing a medicament for the treatment of an inflammatory disease associated with fibrosis, comprising combining a pharmaceutically acceptable carrier and a therapeutic amount of the compound or a pharmaceutically acceptable salt thereof according to claim 1 .

11. A method of treating an inflammatory disease associated with fibrosis, comprising administering the compound or a pharmaceutically acceptable salt thereof according to claim 1 to a patient in need thereof.

12. A therapeutic agent for the treatment of cancer, comprising a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient:

wherein m represents an integer of 0 to 2, and n represents an integer of 0 to 1, provided that 0≤m+n≤2;
R 1 represents a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted amino group;
R 2 represents an optionally substituted fluorenyl group, a substituted naphthyl group, or an optionally substituted group represented by any one of the following structures:

R 3 represents 0 to 7 identical or different substituents attached to the naphthyl group; and
X represents a single bond, —CH 2 — group, or —NH— group.

13. The therapeutic agent according to claim 12 , wherein the cancer is colon cancer or prostate cancer.

14. The therapeutic agent according to claim 12 , further comprising an active ingredient of at least one additional drug for the treatment of cancer.

15. A method of treating cancer, comprising administering the therapeutic agent according to claim 12 , in combination with at least one additional drug for the treatment of cancer.

16. A method of preparing a medicament for the treatment of cancer, comprising combining a pharmaceutically acceptable carrier and a therapeutic amount of the compound or a pharmaceutically acceptable salt thereof according to claim 1 .

17. A method of treating cancer, comprising administering the compound or a pharmaceutically acceptable salt thereof according to claim 1 to a patient in need thereof.

18. A therapeutic agent for the treatment of obesity, comprising a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient:

wherein m represents an integer of 0 to 2, and n represents an integer of 0 to 1, provided that 0≤m+n≤2;
R 1 represents a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted amino group;
R 2 represents an optionally substituted fluorenyl group, a substituted naphthyl group, or an optionally substituted group represented by any one of the following structures:

R 3 represents 0 to 7 identical or different substituents attached to the naphthyl group; and
X represents a single bond, —CH 2 — group, or —NH— group.

19. The therapeutic agent according to claim 18 , further comprising an active ingredient of at least one additional drug for the treatment of obesity.

20. A method of treating obesity, comprising administering the therapeutic agent according to claim 18 , in combination with at least one additional drug for the treatment of obesi

Assignees

• Univ Hiroshima
• Tokyo Univ Of Pharmacy & Life Sciences
• Univ Tokyo

Inventors

• Asano Tomoichiro
• NAKATSU Yusuke
• Ito Hisanaka
• Okabe Takayoshi

Classifications

• A61K31/216

  of acids having aromatic rings, e.g. benactizyne, clofibrate · CPC title

• A61K31/538 Primary

  ortho- or peri-condensed with carbocyclic ring systems · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• C07C271/22 Primary

  to carbon atoms of hydrocarbon radicals substituted by carboxyl groups · CPC title

• C07D209/82

  Carbazoles; Hydrogenated carbazoles · CPC title