Adenosine 2 receptor antagonists
The instant disclosure provides novel adenosine receptor antagonist compounds, compositions, methods of making and methods of using. In a further aspect, a method of treating a subject in need thereof, comprising administering a therapeutically effective amount of any one or more of the compounds described herein. In some embodiments, the subject has cancer and the method is a method of treating cancer.
1. A compound having a formula:
wherein R, in each instance, is independently selected from H and D;
R 1 is selected from —CH 3 and —CD 3 ;
R 2 is selected from the group consisting of H, F, Cl, —CF 3 , —OCH 3 , and —OCD 3 ;
R 3 is selected from hydrogen, —CH 3 , —CD 3 , and —CF 3 ;
R 4 and R 5 are each selected from H, D, or combine with the intervening atoms to form a 5-membered ring;
X 1 , X 2 and X 3 are independently selected from —N— and —CH—; and
Y is selected from —CH— and —N—
wherein the compound is an adenosine A 2A receptor (A 2A R) selective antagonist.
2. The compound of claim 1 , having the formula selected from:
3. The compound of claim 1 , having the following formula:
wherein:
X 1 , X 2 and X 3 are independently selected from —N— and —CH—;
R 2 is selected from the group consisting of H, F, Cl, —CF 3 , —OCH 3 , and —OCD 3 ; and
R 3 is selected from —CH 3 , —CD 3 , and —CF 3 .
4. The compound of claim 3 , having the formula selected from:
5. The compound of claim 1 , having the following formula:
wherein:
R 2 is selected from the group consisting of F, Cl, —CF 3 , —OCH 3 , and —OCD 3 ; and
R 3 is selected from —CH 3 , —CD 3 , and —CF 3 .
6. The compound of claim 5 , having the formula selected from:
7. The compound of claim 1 , having the following formula:
wherein:
one of X 1 or X 2 is —N— and the other of X 1 or X 2 is —CH—;
R 2 is selected from the group consisting of F, Cl, and —CF 3 ; and
R 3 is selected from —CH 3 , —CD 3 , and —CF 3 .
8. The compound of claim 7 , having the formula selected from:
9. The compound of claim 1 , having the following formula:
wherein:
X 1 is selected from —N— and —CH—;
R 2 is selected from the group consisting of H, F, Cl, —CF 3 , —OCH 3 , and —OCD 3 .
10. The compound of claim 9 , having the formula:
11. The compound of claim 1 , having the following formula:
wherein:
R, in each instance, is independently selected from H and D;
R 1 is selected from —CH 3 and —CD 3 ;
R 3 is selected from —CH 3 and —CD 3 ; and
R 4 and R 5 are each selected from H and D.
12. The compound of claim 11 , having the formula selected from:
13. The compound of claim 1 , wherein the compound is a pharmaceutically acceptable salt.
14. A metabolite of the compound of claim 1 .
15. A composition comprising:
a compound having a formula:
wherein R, in each instance, is independently selected from H and D;
R 1 is selected from —CH 3 and —CD 3 ;
R 2 is selected from the group consisting of H, F, Cl, —CF 3 , —OCH 3 , and —OCD 3 ;
R 3 is selected from hydrogen, —CH 3 , —CD 3 , and —CF 3 ;
R 4 and R 5 are each selected from H, D, or combine with the intervening atoms to form a 5-membered ring;
X 1 , X 2 and X 3 are independently selected from —N— and —CH—; and
Y is selected from —CH— and —N—;
wherein the compound is an adenosine A 2A receptor (A 2A R) selective antagonist and
a pharmaceutically acceptable excipient.
16. A dosage form comprising the composition of claim 15 .
17. A method of treating a subject suffering from cancer, comprising:
administering to the subject a therapeutically effective amount of a compound having a formula:
wherein R, in each instance, is independently selected from H and D;
R 1 is selected from —CH 3 and —CD 3 ;
R 2 is selected from the group consisting of H, F, Cl, —CF 3 , —OCH 3 , and —OCD 3 ;
R 3 is selected from hydrogen, —CH 3 , —CD 3 , and —CF 3 ;
R 4 and R 5 are each selected from H, D, or combine with the intervening atoms to form a 5-membered ring;
X 1 , X 2 and X 3 are independently selected from —N— and —CH—; and
Y is selected from —CH— and —N—
wherein the compound is an adenosine A 2A receptor (A 2A R) selective antagonist.