ATF6 modulators and uses thereof
Compounds (1-2) as modulators of Activating Transcription Factor 6 (ATF6) are provided. The compounds may find use as therapeutic agents for the treatment of diseases or disorders mediated by ATF6 and may find particular use in the treatment of viral infections, neurodegenerative diseases, vascular diseases, or cancer. (Formula (1-2))
1 . A compound of formula (I-1):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is H, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, or C 1 -C 6 haloalkyl;
n is 0 or 1;
L is —CH 2 — or is absent;
B is —CH 2 CH 2 —, —CH═CH—, or —C═C—;
R 2 , R 3 , R 4 , R 5 , and R 6 are each independently H, halo, CN, —OH, —NH 2 , C 1-6 alkoxy, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
or R 2 , R 4 , R 5 , and R 6 are each independently H, halo, CN, —OH, —NH 2 , C 1-6 alkoxy, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl and R 3 is taken together with R 1 and the atoms to which they are attached to form a 5- or 6-membered carbocyclic ring, wherein the 5- or 6-membered carbocyclic ring is unsubstituted or substituted with one to three groups selected from the group consisting of halo, CN, —OH, C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl;
A is
R a is 5- or 6-membered heteroaryl, wherein the 5- or 6-membered heteroaryl is unsubstituted or substituted with one to four groups selected from the group consisting of OH, halo, C 1 -C 6 alkyl and C 1 -C 6 alkoxy,
R 7 is H, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; and
R 8 is H or C 1 -C 6 alkyl.
2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the 5- or 6-membered heteroaryl of R a is selected from the group consisting of 2-furyl, 2-pyridinyl, 2-pyrimidinyl, 4-pyrimidinyl, and 2-pyrazinyl.
3 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 1, R 1 is H and L is absent.
4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 and R 8 are H.
5 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein B is —CH═CH—, or —C═C—.
6 . A compound selected from the group consisting of:
2-1
2-2
Isomer A of Compound 1
2-3
2-4
2-5
2-6
2-7
Isomer A of Compound 6
2-8
Isomer B of Compound 6
2-9
2-10
2-11
2-12
2-13
2-14
2-15
2-16
2-17
2-18
2-19
2-20
2-21
Isomer A of compound 2-10
2-22
Isomer B of compound 2-10
2-23
Isomer A of compound 2-11
2-24
Isomer B of compound 2-11
or a pharmaceutically acceptable salt thereof.