Arginase inhibitors and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12435097-B2
Application number	US-202017429011-A
Country	US
Kind code	B2
Filing date	Feb 7, 2020
Priority date	Feb 8, 2019
Publication date	Oct 7, 2025
Grant date	Oct 7, 2025

Abstract

Disclosed are compounds of formula (Ib) or (Vc), or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of formula (Ib) or (Vc) and methods of using the same for treating cancer, respiratory inflammatory disease, and inhibiting arginase; wherein R 1 is —H or —C(O)CH(R 1a )NHR 1b ; and R 1a is selected from —H, —(C 1 -C 4 ) alkyl and CH 2 OR 1c ; R 1b is —H; or alternatively, R 1a and R 1b , together with the atom to which they are attached, form a 5-membered heterocyclic ring; and R 1c is H or —CH 3 .

First claim

The invention claimed is:

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof:

wherein
R 1 is —H or —C(O)CH(R 1a )NHR 1b ; and
R 1a is selected from —H, —(C 1 -C 6 ) alkyl and CH 2 OR 1c ;

R 1b is —H; or alternatively, R 1a and R 1b , together with the atom to which they are attached, form a 5-membered heterocyclic ring; and
R 1c is H or —CH 3 .

2. The compound of claim 1 represented by formula (II), or a pharmaceutically acceptable salt thereof:

wherein
R 2 is —H or —C(O)CH(R 2a )NH 2 ; and
R 2a is selected from —H or —(C 1 -C 6 ) alkyl.

3. The compound of claim 1 represented by formula (III), or a pharmaceutically acceptable salt thereof:

wherein
R 3 is selected from —H or —(C 1 -C 4 ) alkyl.

4. The compound of claim 1 represented by formula (IV), or a pharmaceutically acceptable salt thereof:

5. A compound of formula (V), or a pharmaceutically acceptable salt thereof:

wherein
R 1 is —H or —C(O)CH(R 1a )NHR 1b ; and
R 1a is selected from —H, —(C 1 -C 4 ) alkyl and CH 2 OR 1c ;

R 1b is —H; or alternatively, R 1a and R 1b , together with the atom to which they are attached, form a 5-membered heterocyclic ring; and
R 1c is H or —CH 3 .

6. The compound of claim 5 represented by formula (VI), or a pharmaceutically acceptable salt thereof:

wherein
R 2 is —H or —C(O)CH(R 2a )NH 2 ; and
R 2a is selected from —H or —(C 1 -C 6 ) alkyl.

7. The compound of claim 5 represented by formula (VII), or a pharmaceutically acceptable salt thereof:

wherein
R 3 is selected from —H or —(C 1 -C 4 ) alkyl.

8. The compound of claim 5 represented by formula (VIII), or a pharmaceutically acceptable salt thereof:

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

10. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

11. A method of treating cancer in a patient comprising administering to the patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

12. A method of treating respiratory inflammatory disease in a patient comprising administering to the patient a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising a compound of claim 5 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

14. A method of treating cancer in a patient comprising administering to the patient a therapeutically effective amount of a compound of claim 5 , or a pharmaceutically acceptable salt thereof.

15. A method of treating respiratory inflammatory disease in a patient comprising administering to the patient a compound of claim 5 , or a pharmaceutically acceptable salt thereof.

Assignees

• Astrazeneca Ab

Inventors

• Mlynarski Scott Nathan
• Grebe Tyler
• Kawatkar Sameer
• Finlay Maurice Raymond Verschoyle
• Simpson Iain

Classifications

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/69

  Boron compounds · CPC title

• C07F5/025 Primary

  Boronic and borinic acid compounds · CPC title