Pyrazolo[1,5-a]pyrimidine-based compounds, compositions comprising them, and methods of their use
View Patent ↗Pyrazolo[1,5-a]pyrimidine-based compounds of the formula: are disclosed, wherein R 1 , R 2 and R 3 are defined herein. Compositions comprising the compounds and methods of their use to treat, manage and/or prevent diseases and disorders mediated by adaptor associated kinase 1 activity are also disclosed.
1. A compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X is CH or N;
each R 1A is independently —OR 1C , —N(R 1C ) 2 , —C(O)R 1C , —C(O)OR 1C , —C(O)N(R 1C ) 2 , —N(R 1C )C(O)OR 1C , cyano, halo, or optionally substituted C 1-12 hydrocarbyl or 2-12-membered heterocarbyl, which optional substitution is with one or more R 1B ;
each R 1B is independently —OR 1C , —N(R 1C ) 2 , —C(O)R 1C , —C(O)OR 1C , —C(O)N(R 1C ) 2 , —N(R 1C )C(O)OR 1C , cyano or halo;
each R 1C is independently hydrogen or optionally substituted C 1-12 hydrocarbyl or 2-12-membered heterocarbyl, which optional substitution is with one or more of cyano, halo or hydroxyl;
each R 2C is independently —OR 2D , —N(R 2D ) 2 , —C(O)R 2D , —C(O)OR 2D , —C(O)N(R 2D ) 2 , —N(R 2D )C(O)OR 2D , cyano, halo, or optionally substituted C 1-12 hydrocarbyl or 2-12-membered heterocarbyl, which optional substitution is with one or more amino, cyano, halo, hydroxyl, or R 2D ;
each R 2D is independently hydrogen or optionally substituted C 1-12 hydrocarbyl or 2-12-membered heterocarbyl, which optional substitution is with one or more of amino, cyano, halo, hydroxyl; and
m is 0-3.
2. The compound of claim 1 , which is of the formula:
3. The compound of claim 2 , which is of the formula:
4. The compound of claim 2 , which is of the formula:
5. The compound of claim 1 , wherein at least one R 1A , is halo.
6. The compound of claim 1 , wherein at least one R 1A is —OR 1C .
7. The compound of claim 6 , wherein R 1C is optionally substituted C 1-12 hydrocarbyl.
8. The compound of any of claim 1 , wherein R 2C is —C(O)OR 2D , —C(O)N(R 2D ) 2 , or —N(R 2D )C(O)OR 2D .
9. The compound of claim 1 , wherein R 2C is —C(O)R 2D .
10. The compound of claim 8 , wherein each R 2D is independently hydrogen or C 1-12 hydrocarbyl.
11. The compound of claim 8 , wherein at least one R 2D is optionally substituted C 1-12 hydrocarbyl, which optional substitution is with one or more of amino, cyano, halo, hydroxyl.
12. The compound of claim 8 , wherein R 2D is 2-12-membered heterocarbyl comprising at least one nitrogen atom.
13. The compound of claim 9 , wherein R 2D is independently hydrogen or 1-12 hydrocarbyl.
14. The compound of claim 9 , wherein R 2D is optionally substituted C 1-12 hydrocarbyl, which optional substitution is with one or more of amino, cyano, halo, hydroxyl.
15. The compound of claim 9 , wherein R 2D is 2-12-membered heterocarbyl comprising at least one nitrogen atom.