Substituted 1H-indole-2-carboxamide compounds as indoleamine-2,3-dioxygenase inhibitors
View Patent ↗Provided is a compound having formula (I): wherein R 2 is selected from —C 1 , —Br and —CN; R 1 and R 4 are independently selected from H and —F; R 631 , R 632 , R 641 and R 642 are independently selected from —H, —F and substituted or unsubstituted C 1 -C 3 alkyl groups; and R 651 and R 652 are independently selected from H and substituted or unsubstituted C 1 -C 3 alkyl groups and substituted or unsubstituted phenyl groups; and wherein at least one of R 631 , R 632 , R 641 , R 642 and R 652 is not —H, or wherein when all of R 631 , R 632 , R 641 , R 642 and R 652 are —H, R 651 is not Me or Et.
1. A compound of formula (I), or a pharmaceutically acceptable salt thereof:
wherein R 2 is selected from Cl, —Br and —CN;
R 1 and R 4 are independently selected from —H and —F;
R 631 , R 632 , R 641 and R 642 are independently selected from —H, —F and C 1 -C 3 alkyl;
R 651 and R 652 are independently selected from —H, and C 1 -C 3 alkyl; and
wherein at least one of R 631 , R 632 , R 641 , and R 642 is not —H.
2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, which compound is a compound of the following formula:
3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, which compound is a compound of the following formula:
4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, which compound is a compound of the following formula:
wherein R 642 is methyl or ethyl.
5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, which compound is a compound of one of the following formulae:
6. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, which compound is an isolated enantiomer or a racemic mixture of one or both of the following formula:
wherein R 642 is a sterically larger group than any of R 631 , R 632 and R 641 .
7. The compound according to claim 1 , which compound is an isolated enantiomer or a racemic mixture of one or both of the following formulae:
or one or both of one of the following formulae:
or one or both of one of the following formulae:
8. The compound according to claim 1 , which is an isolated enantiomer, a racemic mixture or an achiral compound of any of the following formulae:
isolated (+) and (−) enantiomers and racemic mixture 1: [(+) 1, (−) 1 and rac 1],
isolated (+) and (−) enantiomers and racemic mixture 2: [(+) 2, (−) 2 and rac 2],
isolated (+) and (−) enantiomers and racemic mixture 7: [(+) 7, (−) 7 and rac 7],
9. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutical excipient.
10. The pharmaceutical composition according to claim 9 , further comprising a pharmaceutically acceptable additive.
11. The pharmaceutical composition according to claim 10 , further comprising an agent selected from: an anti-tumour vaccine; a cancer immunotherapy treatment; an immunomodulator; an immunosuppressant; a cytokine therapy; a tyrosine kinase inhibitor; and a chimeric antigen receptor T cell therapy (CAR-T).