US 12,071,411 B2
Inhibitors of HIF-2α and methods of use thereof
Joel Worley Beatty, San Mateo, CA (US); Samuel Lawrie Drew, Millbrae, CA (US); Matthew Epplin, San Francisco, CA (US); Jeremy Fournier, Fremont, CA (US); Balint Gal, Hayward, CA (US); Clayton Hardman, San Francisco, CA (US); Artur Karenovich Mailyan, Livermore, CA (US); Kenneth Victor Lawson, San Francisco, CA (US); Manmohan Reddy Leleti, Dublin, CA (US); Dongdong Liu, Fremont, CA (US); Guillaume Mata, Berkeley, CA (US); Masa Podunavac, Hayward, CA (US); Jay Patrick Powers, Sisters, OR (US); Brandon Reid Rosen, San Mateo, CA (US); and Kai Yu, Hayward, CA (US)
Assigned to Arcus Biosciences, Inc., Hayward, CA (US)
Filed by ARCUS BIOSCIENCES, INC., Hayward, CA (US)
Filed on Oct. 28, 2022, as Appl. No. 18/050,557.
Claims priority of provisional application 63/380,221, filed on Oct. 19, 2022.
Claims priority of provisional application 63/345,120, filed on May 24, 2022.
Claims priority of provisional application 63/273,283, filed on Oct. 29, 2021.
Prior Publication US 2023/0159466 A1, May 25, 2023
Int. Cl. C07D 231/56 (2006.01); C07D 405/04 (2006.01); C07D 405/06 (2006.01); C07D 409/04 (2006.01); C07D 409/06 (2006.01); C07D 413/06 (2006.01)
CPC C07D 231/56 (2013.01) [C07D 405/04 (2013.01); C07D 405/06 (2013.01); C07D 409/04 (2013.01); C07D 409/06 (2013.01); C07D 413/06 (2013.01)] 31 Claims
 
1. A compound, or a pharmaceutically acceptable salt thereof, having a structure according to Formula I:

OG Complex Work Unit Chemistry
wherein:
n is 1 or 2;
m is 2, 3, 4, 5, 6, 7, or 8, provided that when n is 1, m is 2, 3, 4, 5, or 6;
each R1 is independently selected from the group consisting of halo, —OH, and —O—(C1-C3 alkyl);
R2 is selected from the group consisting of —C1-C6 alkyl, —CN, and —S(O)2—(C1-C3 alkyl), wherein the —C1-C6 alkyl and —S(O)2—(C1-C3 alkyl) are substituted with 0-3 halo;
R3 is selected from the group consisting of —C1-C2 alkyl substituted with 1-3 R4, —C3-C6 alkyl, —C3-C8 cycloalkyl, -3- to 7-membered heterocycloalkyl having 1-3 heteroatom or heteroatom groups selected from N, O, S, S(═O), and S(═O)2, —Y—(C3-C6 cycloalkyl), —Y—O—(C3-C6 cycloalkyl), —Y-(3- to 6-membered heterocycloalkyl) having 1-3 heteroatom or heteroatom groups selected from N, O, S, S(═O), and S(═O)2, —X-(phenyl), and —Y-(5- to 6-membered heteroaryl) having 1-3 heteroatoms selected from N, O, and S, wherein the —C3-C6 alkyl, —C3-C8 cycloalkyl, -3- to 7-membered heterocycloalkyl, —Y—(C3-C6 cycloalkyl), —Y—O—(C3-C6 cycloalkyl), —Y-(3- to 6-membered heterocycloalkyl), —X-(phenyl), and —Y-(5- to 6-membered heteroaryl), are independently substituted with 0-3 R4;
each R4 is independently selected from halo, —C1-C6 alkyl, —CN, —C1-C6 haloalkyl, —OH, —O—(C1-C6 alkyl), —Y—O—(C1-C6 alkyl), —S—(C1-C6 alkyl), —S(O)—(C1-C6 alkyl), and —S(O)2—(C1-C6 alkyl), wherein the —O—(C1-C6 alkyl), —Y—O—(C1-C6 alkyl), —S—(C1-C6 alkyl), —S(O)—(C1-C6 alkyl), and —S(O)2—(C1-C6 alkyl) are independently substituted with 0-3 halo;
X is —C2-C3 alkylene-; and
Y is —C1-C3 alkylene-.