Modulators of aldehyde dehydrogenase activity and methods of use thereof
The present invention provides compounds that function as modulators of aldehyde dehydrogenase activity; and pharmaceutical compositions comprising the compounds. The present invention provides therapeutic methods involving administering a subject compound, or a subject pharmaceutical composition.
1. A compound of Formula I:
wherein each of R 1 , R 2 , and R 3 is independently selected from H; a halo; a substituted or unsubstituted phenyl group; an aliphatic group; an alkyl group; a substituted alkyl group; an alkenyl group; an alkynyl group; a substituted or unsubstituted cyclic group; a substituted or unsubstituted heterocyclic group; a substituted or unsubstituted aryl group; and a substituted or unsubstituted heteroaryl group;
wherein A is C or S and where a=1 when A=C; and where a=2 when A=S; and
wherein Ar 1 is a benzodioxole and Ar 2 is a substituted pyridine oxide;
or a pharmaceutically acceptable salt, an analog, or a derivative thereof.
2. The compound of claim 1 , wherein the substituted pyridine oxide is selected from
wherein R 9 to R 12 is each independently selected H; a halo; an aliphatic group; an alkyl group; a substituted alkyl group; an alkenyl group; an alkynyl group; a substituted or unsubstituted cyclic group; an ether; a substituted or unsubstituted amine; an ester; and an amide group.
3. The compound of claim 1 , wherein the compound is of Formula Ia:
wherein X n and X y are each independently O;
wherein . . . (dotted line) is a bond;
wherein z is the integer 1;
wherein n is the integer 1;
wherein y is the integer 1;
wherein A=C or S, and where a=1 when A=C; and where a=2 when A=S;
wherein Ar is independently a substituted pyridine oxide of a formula selected from:
wherein R 9 to R 12 is each independently selected from H; a halo; an aliphatic group; an alkyl group; a substituted alkyl group; an alkenyl group; an alkynyl group; a substituted or unsubstituted cyclic group; an ether; a substituted or unsubstituted amine; an ester; and an amide group.
4. A compound of Formula II:
wherein X n and X y are each independently O; where n is the integer 1; where y is the integer 1;
wherein . . . (dotted line) is a bond; where z is the integer 1;
wherein A is C or S, and where a=1 when A=C; and where a=2 when A=S;
wherein Ar is a substituted pyridine oxide; and
wherein R 1 to R 6 is each independently selected from H; a halo; a substituted or unsubstituted phenyl group; an aliphatic group; an alkyl group; a substituted alkyl group; an alkenyl group; an alkynyl group; a substituted or unsubstituted cyclic group; a substituted or unsubstituted heterocyclic group; a substituted or unsubstituted aryl group; and a substituted or unsubstituted heteroaryl group;
or a pharmaceutically acceptable salt, an analog, or a derivative thereof.
5. The compound of claim 4 , wherein the substituted pyridine oxide is of a formula selected from:
wherein R 9 to R 12 is each independently selected from H; a halo; an aliphatic group; an alkyl group; a substituted alkyl group; an alkenyl group; an alkynyl group; a substituted or unsubstituted cyclic group; an ether; a substituted or unsubstituted amine; an ester; and an amide group.
6. A compound of Formula a:
wherein R 1 to R 4 is each independently selected from H; a halo; an aliphatic group; an alkyl group; a substituted alkyl group; an alkenyl group; an alkynyl group; a substituted or unsubstituted cyclic group; an ether; a substituted or unsubstituted amine; an ester; and an amide group;
or a pharmaceutically acceptable salt, an analog, or a derivative thereof.
7. The compound of claim 6 , wherein the compound has a structure selected from:
or a pharmaceutically acceptable salt, an analog, or a derivative thereof.
8. A compound of Formula b:
wherein R 1 to R 4 is each independently selected from H; a halo; an aliphatic group; an alkyl group; a substituted alkyl group; an alkenyl group; an alkynyl group; a substituted or unsubstituted cyclic group; an ether; a substituted or unsubstituted amine; an ester; and an amide group;
or a pharmaceutically acceptable salt, an analog, or a derivative thereof.
9. The compound of claim 8 , wherein the compound has a structure selected from:
or a pharmaceutically acceptable salt, an analog, or a derivative thereof.
10. A compound of Formula c:
wherein R 1 to R 4 is each independently selected from such group, but not limit to, H; a halo; an aliphatic group; an alkyl group; a substituted alkyl group; an alkenyl group; an alkynyl group; a substituted or unsubstituted cyclic group; an ether; a substituted or unsubstituted amine; an ester; and an amide group;
or a pharmaceutically acceptable salt, an analog, or a derivative thereof.
11. The compound of claim 10 , wherein the compound has a structure selected from:
or a pharmaceutically acceptable salt, an analog, or a derivative thereof.
12. The compound of claim 2 , wherein the halo is bromo, fluoro, chloro or iodo.
13. The compound of claim 10 , wherein the halo is bromo, fluoro, chloro or iodo.
14. A pharmaceutical composition comprising:
a) a compound of one of claims 1 , 4 , 6 , 8 , and 10 ; and
b) a pharmaceutically acceptable excipient.