Arginase inhibitors and methods of use thereof
Disclosed are compounds of formula (Ia) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of formula (Ia) and methods of using the same for treating cancer or a respiratory inflammatory disease and inhibiting arginase: wherein R 1 is —NHR 1a ; R 1a is —H or —C(O)CH(R 1b )NHR 1c ; and R 1b is selected from —H, —(C 1 -C 4 ) alkyl and CH 2 OR 1d and R 1c is —H; or R 1b and R 1c , together with the atom to which they are attached, form a 5-membered heterocyclic ring; and R 1d is H or —CH 3 .
1. A compound of formula (II), or a pharmaceutically acceptable salt thereof:
wherein
R 2 is —OH or —NHR 2a ;
R 2a is —H or —C(O)CH(R 2b )NH 2 ; and
R 2b is —CH 3 or —CH(CH 3 ) 2 .
2. The compound of claim 1 represented by formula (III), or a pharmaceutically acceptable salt thereof:
wherein R 3 is —CH 3 or —CH(CH 3 ) 2 .
3. A compound of formula (IIb), or a pharmaceutically acceptable salt thereof:
wherein
R 2 is —OH or —NHR 2a ;
R 2a is —H or —C(O)CH(R 2b )NH 2 ; and
R 2b is —CH 3 or —CH(CH 3 ) 2 .
4. The compound of claim 3 represented by formula (IIIb), or a pharmaceutically acceptable salt thereof:
wherein R 3 is —CH 3 or —CH(CH 3 ) 2 .
5. The compound of claim 1 selected from:
or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1 , having the following structure
or a pharmaceutically acceptable salt thereof.
7. The compound of claim 1 , having the following structure
8. The compound of claim 1 , having the following structure
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 1 , having the following structure
10. The compound of claim 3 , having the following structure
or a pharmaceutically acceptable salt thereof.
11. The compound of claim 3 , having the following structure
12. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
13. A pharmaceutical composition comprising a compound of claim 3 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.