Cyclic peptide compound having Kras inhibitory action

Patent metadata

Field	Value
Publication number	US-12371454-B2
Application number	US-202418773066-A
Country	US
Kind code	B2
Filing date	Jul 15, 2024
Priority date	Nov 7, 2019
Publication date	Jul 29, 2025
Grant date	Jul 29, 2025

Abstract

The present inventors found cyclic peptide compounds that interact with Ras, and non-natural amino acids useful for the production of the cyclic peptide compounds. The inventors also found that the cyclic peptide compounds inhibit the binding between Ras and SOS. In addition, the inventors found specific non-natural amino acids contained in the cyclic peptide compounds and methods for production thereof.

First claim

The invention claimed is:

1. A compound, which is (5S,8S,11S,15S,18S,23aS,29S,35S,37aS)-8-((S)-sec-butyl)-18-cyclopentyl-29-(3,5-difluoro-4-(trifluoromethyl) phenethyl)-36-ethyl-11-isobutyl-N,N,5,6,12,16,19,33-octamethyl-35-(4-methylbenzyl)-4,7,10,13,17,20,23,28,31,34,37-undecaoxotetratriacontahydro-2H,4H-spiro[azeto[2,1-u]pyrrolo[2,1-i][1,4,7,10,13,16,19,22,25,28,31]undecaazacyclotetratriacontine-21,1′-cyclopentane]-15-carboxamide.

2. A solvate of (5S,8S,11S,15S,18S,23aS,29S,35S,37aS)-8-((S)-sec-butyl)-18-cyclopentyl-29-(3,5-difluoro-4-(trifluoromethyl)phenethyl)-36-ethyl-11-isobutyl-N,N,5,6,12,16,19,33-octamethyl-35-(4-methylbenzyl)-4,7,10,13,17,20,23,28,31,34,37-undecaoxotetratriacontahydro-2H,4H-spiro[azeto[2,1-u]pyrrolo[2,1-i][1,4,7,10,13,16,19,22,25,28,31]undecaazacyclotetratriacontine-21,1′-cyclopentane]-15-carboxamide.

3. The solvate according to claim 2 , which is a hydrate.

4. A pharmaceutical composition comprising the compound of claim 1 .

5. A pharmaceutical composition comprising the solvate of claim 2 .

6. A pharmaceutical composition comprising the solvate of claim 3 .

7. A method of treating cancer in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of the compound of claim 1 , wherein the cancer is pancreatic cancer.

8. The method of claim 7 , wherein the subject is human.

9. A method of treating cancer in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of the solvate of claim 2 , wherein the cancer is pancreatic cancer.

10. The method of claim 9 , wherein the subject is human.

11. A method of treating cancer in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of the solvate of claim 3 , wherein the cancer is pancreatic cancer.

12. The method of claim 11 , wherein the subject is human.

Assignees

• Chugai Pharmaceutical Co Ltd

Inventors

• Tanada Mikimasa
• Takano Koji
• Matsuo Atsushi
• Tamiya Minoru
• Chiyoda Aya
• Ito Toshiya
• Iida Takeo

Classifications

• C07F5/025

  Boronic and borinic acid compounds · CPC title

• C07D409/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D333/28

  Halogen atoms · CPC title

• C07D309/12

  only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers · CPC title

• C07D295/15

  to an acyclic saturated chain · CPC title