Inhibitors of fibroblast activation protein alpha
Disclosed are peptide-based compounds that include boronic acid or cyano functionality, which efficiently and selectively inhibit fibroblast activation protein alpha. Among other therapeutic utilities, the peptide-based compounds may be useful for the treatment of cancer.
1. A compound having a structure of formula (I)
wherein
L is absent;
R 1 is C 1-6 heteroaracyl;
R 2 is selected from the group consisting of H and C 1-6 alkyl;
R 3 is selected from the group consisting of H, C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 thioalkyl, and C 1-6 aralkyl;
W is B(Y 1 )(Y 2 ); and
Y 1 and Y 2 are independently OH.
2. The compound of claim 1 , wherein R 3 is C 1-6 alkyl.
3. The compound of claim 1 , wherein C 1-6 heteroaracyl is a C 1-6 acyl substituted with a heteroaryl selected from the group consisting of pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazome, pyridine, pyrazine, pyridazine, and pyrimidine.
4. The compound of claim 1 , wherein R 2 is H; and R 3 is C 1-6 alkyl.
5. The compound of claim 1 , wherein C 1-6 heteroaracyl is a —C(O)-heteroaryl, wherein heteroaryl is selected from the group consisting of pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazome, pyridine, pyrazine, pyridazine, and pyrimidine.
6. A pharmaceutical composition suitable for administration to a patient, comprising a compound of claim 1 ; and a pharmaceutically acceptable diluent or carrier.
7. A pharmaceutical composition suitable for administration to a patient, comprising a compound of claim 5 ; and a pharmaceutically acceptable diluent or carrier.