Treatment of pulmonary and other conditions
Disclosed is a compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of: X 1 -L-X 2 wherein L is a linking moiety comprising an enone; and X 1 and X 2 are each independently an optionally-substituted N-heterocycle. Also disclosed are method for treating pulmonary conditions and other organ or system conditions with the compounds.
1. A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:
wherein represents a single bond;
A is CH(S—R 5 ), wherein R 5 is an acylamino-substituted carboxylalkyl, a sulfonate-substituted alkyl, or an acylamino-substituted amido; and
X 1 and X 2 are each independently an optionally substituted 6-membered N-heterocycle.
2. The compound of claim 1 , wherein X 1 has a structure of:
and X 2 has a structure of:
wherein Z 1 , Z 2 , and Z 3 are each independently C or N, provided that at least one of Z 1 , Z 2 , or Z 3 is N; and
Y 1 , Y 2 , Y 3 , Y 4 and Y 5 are each independently H, optionally-substituted alkyl, amino, hydroxyl, optionally-substituted alkoxy, optionally-substituted thiol, acyl, or halogen.
3. The compound of claim 1 , wherein the compound has a structure of:
4. The compound of 3 , wherein the compound has a structure of:
wherein Y 2 , Y 3 , Y 4 and Y 5 are each independently H, optionally-substituted alkyl, amino, hydroxyl, optionally-substituted alkoxy, optionally-substituted thiol, acyl, or halogen.
5. The compound of claim 3 , wherein X 1 and X 2 are each optionally-substituted pyrazinyl or optionally-substituted pyrimidinyl.
6. The compound of claim 5 , wherein X 1 and X 2 are each the same.
7. The compound of claim 5 , wherein X 1 and X 2 are each different.
8. The compound of claim 3 , wherein R 5 is an acylamino-substituted carboxylalkyl, a sulfonate-substituted alkyl, or an acylamino-substituted amido.
9. The compound of claim 3 , wherein —S—R 5 is a N-acetylcysteine moiety, a 2-mercaptoethane sulfonate moiety, or a glutathione moiety.
10. A pharmaceutical composition comprising a compound of claim 1 , and at least one pharmaceutically acceptable excipient.
11. The pharmaceutical composition of claim 10 , wherein the composition is in the form of an aerosol.
12. The pharmaceutical composition of claim 10 , wherein the composition is in the form of a dry powder.
13. The compound of claim 4 , wherein R 5 is an acylamino-substituted carboxylalkyl, a sulfonate-substituted alkyl, or an acylamino-substituted amido.
14. The compound of claim 4 , wherein —S—R 5 is a N-acetylcysteine moiety, a 2-mercaptoethane sulfonate moiety, or a glutathione moiety.
15. The compound of claim 1 , wherein the compound has a structure of:
16. The compound of claim 1 , wherein the compound has a structure of:
17. The compound of claim 4 , wherein Y 2 , Y 3 , Y 4 and Y 5 are each independently H.
18. The compound of claim 13 , wherein Y 2 , Y 3 , Y 4 and Y 5 are each independently H.
19. The compound of claim 14 , wherein Y 2 , Y 3 , Y 4 and Y 5 are each independently H.