Arginase inhibitors and methods of use thereof
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 .
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.