Alkylamine-substituted perthiocarbamates as dual precursors to hydropersulfide and carbonyl sulfide
Alkylamine-substituted perthiocarbamates capable of controllable release of hydropersulfides (RSSH) and carbonyl sulfide (COS) and their use in treating or preventing ischemia-reperfusion injury are described.
1. A compound of formula (I):
wherein:
n is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, and 8;
R 1 is selected from the group consisting of branched or unbranched alkyl, heterocycloalkyl, aryl, heteroaryl, a cysteine residue, a N-acetylcysteine residue, a homocysteine residue, a glutathione residue, and:
wherein:
R 4 and R 5 are each independently selected from the group consisting of H, C 1 -C 4 alkyl, and aryl;
R 6 is C 1 -C 4 alkyl or aryl;
R 7 is —OR 8 or —NR 9 R 10 , wherein R 8 , R 9 , and R 10 are each independently selected from the group consisting of H, C 1 -C 4 alkyl, and aryl;
R 2 is selected from the group consisting of H, alkyl, aryl, and a functional group that responds to a stimulus selected from the group consisting of light, a redox reaction, and an enzymatic reaction;
R 3 is selected from the group consisting of H, alkyl, and aryl; and
X − is an anion.
2. The compound of claim 1 , wherein n is an integer selected from the group consisting of 1, 2, and 3.
3. The compound of claim 1 , wherein the compound of formula (I) is:
n is an integer selected from the group consisting of 1, 2, and 3;
R 4 and R 5 are each independently H or C 1 -C 4 alkyl;
R 6 is C 1 -C 4 alkyl or aryl;
R 7 is —OR 8 or —NR 9 R 10 , wherein R 8 , R 9 , and R 10 are each independently selected from the group consisting of H, C 1 -C 4 alkyl, and aryl;
R 2 is selected from the group consisting of H, C 1 -C 4 alkyl, and a functional group that responds to a stimulus selected from the group consisting of light, a redox reaction, and an enzymatic reaction;
R 3 is selected from the group consisting of H, alkyl, and aryl; and
X − is an anion.
4. The compound of claim 3 , wherein the compound of formula (I) is:
wherein:
n is 1 or 2; and
R 2 is H or CH 3 .
5. The compound of claim 4 , wherein the compound is selected from the group consisting of:
6. The compound of claim 1 , wherein X − is selected from the group consisting of Cl − , Br − , (PO 4 ) 3− , CF 3 COO − , CH 3 COO − , and C 6 H 5 COO − .
7. The compound of claim 1 , wherein the functional group that responds to a stimulus selected from the group consisting of light, a redox reaction, and an enzymatic reaction is selected from the group consisting of:
wherein:
X 1 and X 2 are each independently selected from the group consisting of O, NR 14 , and CR 15 R 16 ; wherein R 14 , R 15 , and R 16 are each independently H or branched or unbranched C 1 -C 4 alkyl;
R 11 and R 12 are each independently selected from the group consisting of H, and branched or unbranched alkyl, or R 11 and R 12 together can form a cyclic alkyl or substituted cyclic alkyl; and
R 13 is selected from the group consisting of branched or unbranched alkyl and aryl.
8. The compound of claim 6 , wherein X − is CF 3 COO − and the compound of formula (I) is selected from the group consisting of:
9. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.