Heterocyclic compounds and imaging agents for imaging Huntington protein
Provided herein are certain compounds and imaging agents useful for detecting a disease or condition associated with protein aggregation, compositions thereof, and methods of their use.
1 . A compound of Formula Ila:
or an isotopically enriched analog, pharmaceutically acceptable salt, tautomer, stereoisomer, or a mixture of stereoisomers thereof,
wherein the compound is labeled with one or more positron-emitting radioactive isotopes selected from 11 C, 13 N, 15 O, and 18 F;
R 23 is hydrogen, halo, cyano, hydroxy, amino, alkylamino, dialkylamino, C 1-4 alkyl, C 1 -4haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, or C 3-6 cycloalkyl;
R 3 is methyl;
each of R 11 , R 12 , R 13 , and R 14 is independently hydrogen, halo, cyano, hydroxy, amino, alkylamino, dialkylamino, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, or C 1-4 haloalkoxy;
L is —(C(R 6 ) 2 ) m —, wherein m is 1, 2, 3, or 4;
each R 6 is independently hydrogen, halo, cyano, hydroxy, amino, alkylamino, dialkylamino, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, or C 1-4 haloalkoxy; or
two R 6 , together with any intervening atoms, join to form a 3- to 6-membered ring;
R a is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl;
R b is -L 2 -X 1 ;
L 2 is absent;
X 1 is C 3-10 cycloalkyl, C 6-10 aryl, heteroaryl, or heterocyclyl, wherein X 1 is optionally substituted with 1 to 4 R 4 ; and
each R 4 is independently halo, cyano, hydroxy, amino, alkylamino, dialkylamino, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, or C 1-4 haloalkoxy;
or R a and R b , along with any intervening atoms, form a 3- to 10-membered heterocyclyl ring optionally substituted by 1 to 4 R 4 .
2 . The compound of claim 1 , wherein X 1 is C 6-10 aryl.
3 . The compound of claim 1 , wherein X 1 is heteroaryl or heterocyclyl.
4 . The compound of claim 1 , wherein each R 4 is independently halo, hydroxy, C 1-4 alkyl, C 1-4 haloalkyl, or C 1-4 alkoxy.
5 . The compound of claim 1 , wherein m is 2.
6 . The compound of claim 1 , wherein one of R 11 , R 12 , R 13 , or R 14 is halo.