Indazole derivatives as inhibitors of SARM1
The present disclosure provides compounds of formula (I) and methods useful for inhibiting SARM1 and/or treating and/or preventing axonal degeneration.
1. A compound of Formula II:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is a 5- to 6-membered heteroaryl ring having 1-3 heteroatoms independently selected from oxygen, nitrogen, and sulfur, wherein the 5- to 6-membered heteroaryl ring is optionally substituted with fluorine or methyl;
R 2 is a 5- to 6-membered heteroaryl ring having 1 heteroatom selected from nitrogen and sulfur, or phenyl, wherein the 5- to 6-membered heteroaryl ring or phenyl is optionally substituted with 1-2 groups selected from fluorine and chlorine;
R 4 is hydrogen or methyl;
Q is N;
X, Y and Z are independently CR 5 or a nitrogen atom, provided that no more than two X, Y and Z are nitrogen atoms; and
R 5 is hydrogen or methyl.
2. The compound according to claim 1 , which is selected from:
or a pharmaceutically acceptable salt thereof.
3. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier.
4. A method comprising a step of:
administering a compound according to claim 1 to a subject who (i) has a condition characterized by axonal degeneration or (ii) is at risk of developing a condition characterized by axonal degeneration.
5. A method of treating or preventing axonal degeneration comprising administering to a subject in need thereof a compound according to claim 1 .
6. A method of inhibiting SARM1 comprising contacting a biological sample with a compound according to claim 1 .
7. A pharmaceutical composition comprising a compound according to claim 2 , and a pharmaceutically acceptable carrier.
8. A method comprising a step of:
administering a compound according to claim 2 to a subject who (i) has a condition characterized by axonal degeneration or (ii) is at risk of developing a condition characterized by axonal degeneration.
9. A method of treating or preventing axonal degeneration comprising administering to a subject in need thereof a compound according to claim 2 .
10. A method of inhibiting SARM1 comprising contacting a biological sample with a compound according to claim 2 .