Heterocyclic compounds as triggering receptor expressed on myeloid cells2 agonists and methods of use
The present disclosure provides compounds of Formula I, useful for the activation of Triggering Receptor Expressed on Myeloid Cells 2 (“TREM2”). This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a neurodegenerative disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula I.
1. A compound selected from:
Ex. 3
Ex. 19
Ex. 22
Ex 23
Ex. 28
Ex. 49
Ex. 61
Ex. 77
Ex. 82
Ex. 94
Ex. 107
Ex. 117
Ex. 123
Ex. 124
Ex. 125
Ex. 126
Ex. 128
Ex. 129
Ex. 131
Ex. 133
Ex. 136
Ex. 137
Ex. 146
Ex. 149
Ex. 150
Ex. 151
Ex. 152
Ex. 162
Ex. 165
Ex. 169
Ex. 172
Ex. 243
Ex. 253
Ex. 266
Ex. 267
Ex. 275
Ex. 276
Ex. 279
Ex. 280
Ex. 281
Ex. 282
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
2. The compound of claim 1 , which is:
Ex. 19,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
3. The compound of claim 1 , which is:
Ex. 22,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
4. The compound of claim 1 , which is:
Ex 23,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
5. The compound of claim 1 , which is:
Ex. 49,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
6. The compound of claim 1 , which is:
Ex. 77,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
7. The compound of claim 1 , which is:
Ex. 107,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
8. The compound of claim 1 , which is:
Ex. 123,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
9. The compound of claim 1 , which is:
Ex. 125,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
10. The compound of claim 1 , which is:
Ex. 146,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
11. The compound of claim 1 , which is:
Ex. 172,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
12. The compound of claim 1 , which is:
Ex. 253,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
13. The compound of claim 1 , which is:
Ex. 279,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
14. The compound of claim 1 , which is:
Ex. 280,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
15. The compound of claim 1 , which is:
Ex. 281,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
16. A pharmaceutical composition comprising a compound selected from
Ex. 3
Ex. 19
Ex. 22
Ex 23
Ex. 28
Ex. 49
Ex. 61
Ex. 77
Ex. 82
Ex. 94
Ex. 107
Ex. 117
Ex. 123
Ex. 124
Ex. 125
Ex. 126
Ex. 128
Ex. 129
Ex. 131
Ex. 133
Ex. 136
Ex. 137
Ex. 146
Ex. 149
Ex. 150
Ex. 151
Ex. 152
Ex. 162
Ex. 165
Ex. 169
Ex. 172
Ex. 243
Ex. 253
Ex. 266
Ex. 267
Ex. 275
Ex. 276
Ex. 279
Ex. 280
Ex. 281
Ex. 282
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable excipient.
17. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 19,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
18. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 22,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
19. The pharmaceutical composition of claim 16 , wherein the compound is
Ex 23,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
20. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 49,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
21. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 77,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
22. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 107,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
23. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 123,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
24. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 125,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
25. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 146,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
26. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 172,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
27. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 253,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
28. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 279,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
29. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 280,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
30. The pharmaceutical composition of claim 16 , wherein the compound is
Ex. 281,
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.