Mitochondrial inhibitors to treat human disease
View Patent ↗The present invention relates to inhibitors of mitochondria-associated, granulocyte-macrophage colony stimulating factor signaling molecule (Magmas), and related compositions and uses thereof.
1. A compound of formula (I):
wherein A is
where “a” represents the point of attachment of A to the ring structure of formula (I) and
where R is H, aliphatic, aromatic or heterocyclic; and
wherein D is
where “d” represents the point of attachment of D to the carbon atom of C═O of formula (I); where R 1 , R 2 , R 3 , R 4 and R 5 are independently H, alkyl, aryl, phenyl, heteroaryl, arylalkyl, heterocyclic, alkenyl, allene, Br, Cl, I, F, OH, NO 2 , OCH 3 , OC 2 H 5 , O-alkyl, SH, S-alkyl, NH 2 , or NH-alkyl; and where R 6 is C, O or S;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 having the formula:
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 having the formula:
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 having the formula:
or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , wherein R═H.
6. The compound of claim 1 , wherein alkyl is C1-C3 alkyl.
7. The compound of claim 1 , wherein one or more of R 1 , R 2 , R 3 , R 4 and R 5 is H.
8. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 1 , wherein the compound is labeled with a detectable marker.
10. The compound of claim 9 , wherein the detectable marker is a radioactive marker.
11. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
12. A method for detecting the expression of mitochondria-associated, granulocyte-macrophage colony stimulating factor signaling molecule (Magmas) in a tissue comprising contacting the tissue with the labeled compound of claim 9 .
13. A method for inhibiting mitochondrial activity in a cell or tissue or for inhibiting metabolic activity in a cell or tissue comprising contacting the cell or tissue with the compound of claim 1 .
14. A method of imaging ischemic injury in a subject comprising administering to the subject the compound of claim 9 .