PYRAZOLO[1,5-a]PYRIMIDINE-BASED COMPOUNDS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE
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 mediated by adaptor associated kinase 1 activity are also disclosed.
1 - 24 . (canceled)
25 . A compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
A is cyclic C 1-12 hydrocarbyl or 4-7-membered heterocycle;
D is cyclic C 1-12 hydrocarbyl or 4-7-membered heterocycle bound to C5 by one of its carbon atoms;
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, oxo, 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;
n is 1-3; and
m is 0-3.
26 . (canceled)
27 . (canceled)
28 . (canceled)
29 . (canceled)
30 . The compound of claim 25 , which is of the formula:
wherein X is CH or N.
31 . The compound of claim 30 , which is of the formula:
32 . The compound of claim 30 , which is of the formula:
wherein R 2C is —C(O)R 2D , —C(O)OR 2D , 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 .
33 . The compound of claim 30 , which is of the formula:
34 . The compound of claim 30 , which is of the formula:
wherein R 2C is —C(O)R 2D , —C(O)OR 2D , 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 .
35 . The compound of claim 25 , wherein X is N and m is 1 or 2
36 . The compound of claim 34 , which is of the formula:
37 . The compound of claim 36 , which is of the formula:
38 . The compound of claim 37 , which is of the formula:
39 . The compound of claim 25 , wherein at least one R 1A is halo.
40 . The compound of claim 25 , wherein at least one R 1A is —OR 1C .
41 . The compound of claim 40 , wherein R 1C is optionally substituted C 1-12 hydrocarbyl.
42 . The compound of claim 25 , wherein R 2C is optionally substituted C 1-6 hydrocarbyl.
43 . The compound of claim 25 , wherein each R 2D is independently hydrogen or C 1-12 hydrocarbyl.
44 . The compound of claim 25 , 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.
45 . The compound of claim 25 , wherein R 2D is 2-12-membered heterocarbyl comprising at least one nitrogen atom.
46 - 51 . (canceled)