Spirocycle compounds and methods of making and using same
Provided herein are compounds of the formula: and compositions comprising the same, which are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.
1. A compound having the structure of Formula (I′):
wherein:
Y is —CH 2 —;
R 1 is H or C 1-6 alkyl;
R 2 is H or C 1-6 alkyl;
each R 3 is independently selected from C 1-6 alkyl, halogen, —CN, C 1-6 haloalkyl, —SF 5 , and —OR 7 ;
R 4 is selected from
each R 7 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, and -C 1-6 alkyl-C 3-8 cycloalkyl;
a, b, c, and d are independently 0 or 1;
e is 0, 1, or 2;
w is 0, 1, 2, 3, or 4;
n is 0 or 1;
m is 0 or 1;
p is 0, 1, or 2; and
q is 0, 1, or 2; provided that when q is 0, then p is 2;
or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein R 4 is
3. The compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein R 4 is
4. The compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein R 1 is H.
5. The compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein R 2 is H.
6. The compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are both H.
7. The compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein each R 3 is independently selected from halogen and C 1-6 haloalkyl.
8. The compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein each R 3 is independently selected from C 1-6 haloalkyl.
9. The compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein each R 3 is —CF 3 .
10. The compound of claim 1 , wherein w is 1.
11. The compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein m is 1, n is 1, q is 1, and p is 1.
12. The compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein m is 1, n is 1, q is 0, and p is 2.
13. The compound of claim 1 selected from:
or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or a pharmaceutically acceptable salt thereof.
14. A pharmaceutical composition comprising a compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.
15. A method of treating pain in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, stereoisomer, or a pharmaceutically acceptable salt thereof.