Small molecule BAX inhibitors and uses thereof
Compounds, compositions and method of using these compounds are disclosed for treating a disease or disorder in which it is desirable to inhibit BAX, such as a cardiovascular disease or disorder.
1. A compound having the structure of formula (VII)
wherein
A is phenyl;
B is phenyl;
R1 and R2 are independently none, C1-C5 alkyl, F, Cl, Br, I, CN, NO 2 , NR4 2 , OR4, CF 3 , COOH, COOR4, NHR4, OCR4, SR4, SOR4, or SO 2 R4;
X is F, Cl, Br, I, NR4 2 , or OR4; wherein the bond between X and the main scaffold is a single bond;
Q is
R3 is none, H, C1-C6 alkyl, R4(C═O), or (CH 2 ) p OH;
R4 is H or C1-C3 alkyl;
Y is S, or N;
p is 1-3;
m is 1 and n is 1;
or a pharmaceutically acceptable salt thereof.
2. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is selected from the group consisting of
3. The compound or a pharmaceutically acceptable salt thereof of claim 1 , where R1 and/or R2 are in the para position with respect to the bond to the N atom.
4. A pharmaceutical composition comprising one or more of the compounds of claim 1 , and a pharmaceutically acceptable carrier.
5. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein X is OH or F.
6. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein R3 is none, H, C1-C6 alkyl, or (CH 2 ) p OH.
7. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein R3 is none or H.
8. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein X is OH or F.
9. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein:
R1 and R2 are independently none, C1-C5 alkyl, F, Cl, Br, I, OR4, CF 3 , or CN;
R3 is none, H, C1-C6 alkyl, or (CH 2 ) p OH;
X is F or OH; and
Y is N.
10. The compound or a pharmaceutically acceptable salt thereof of claim 9 , wherein R1 is none and R2 is C1-C5 alkyl, F, Cl, Br, CF 3 or I.
11. The compound or a pharmaceutically acceptable salt thereof of claim 10 , wherein R2 is F, Cl, Br, or CF 3 .
12. The compound or a pharmaceutically acceptable salt thereof of claim 2 , wherein the compound is
13. The compound or a pharmaceutically acceptable salt thereof of claim 2 , wherein the compound is
14. The compound or a pharmaceutically acceptable salt thereof of claim 2 , wherein the compound is
15. The compound or a pharmaceutically acceptable salt thereof of claim 2 , wherein the compound is
16. The pharmaceutical composition of claim 4 , wherein
R1 and R2 are independently none, C1-C5 alkyl, F, Cl, Br, I, OR4, CF 3 , or CN;
R3 is none, H, C1-C6 alkyl, or (CH 2 ) p OH;
X is F or OH; and
Y is N.
17. The pharmaceutical composition of claim 16 , wherein R1 is none and R2 is C1-C5 alkyl, F, Cl, Br, CF 3 or I.
18. The pharmaceutical composition of claim 17 , wherein R2 is F, Cl, Br, or CF 3 .
19. The pharmaceutical composition of claim 4 , wherein the compound is
20. The pharmaceutical composition of claim 4 , wherein the compound is
21. The pharmaceutical composition of claim 4 , wherein the compound is
22. The pharmaceutical composition of claim 4 , wherein the compound is