	US 12,226,405 B2
	Compounds and compositions for inhibiting the activity of HIF2-alpha and their methods of use
Robin Alec Fairhurst, Allschwil (CH); Christine Fritsch, Leymen (FR); Marc Gerspacher, Hägendorf (CH); Jürgen Hans-Hermann Hinrichs, Schopfheim (DE); Jean-Baptiste Georges Armand Langlois, Schlierbach (FR); Catherine Leblanc, Basel (CH); Tengfei Li, Shanghai (CN); Edwige Liliane Jeanne Lorthiois, Niffer (FR); Christophe Mura, Rosenau (FR); Cristina Montserrat Nieto-Oberhuber, Binningen (CH); Milen Todorov, Rosenau (FR); Andrea Vaupel, Riehen (CH); Nicolas Warin, Blotzheim (FR); and Rainer Wilcken, Basel (CH)
Assigned to Novartis AG, Basel (CH)
Filed by Novartis AG, Basel (CH)
Filed on Apr. 27, 2021, as Appl. No. 17/241,981.
Claims priority of application No. PCT/CN2020/087831 (WO), filed on Apr. 29, 2020.
Prior Publication US 2022/0401422 A1, Dec. 22, 2022
Int. Cl. A61K 31/437 (2006.01); A61K 31/155 (2006.01); A61K 31/436 (2006.01); A61K 31/4375 (2006.01); A61K 31/4747 (2006.01); A61K 31/519 (2006.01); A61K 31/53 (2006.01); A61K 31/5377 (2006.01); A61K 31/635 (2006.01); A61K 31/675 (2006.01); A61P 35/00 (2006.01); C07D 471/10 (2006.01); C07D 471/20 (2006.01); C07D 491/20 (2006.01); C07D 491/22 (2006.01); C07D 495/20 (2006.01); C07D 495/22 (2006.01)

CPC A61K 31/437 (2013.01) [A61K 31/155 (2013.01); A61K 31/436 (2013.01); A61K 31/4375 (2013.01); A61K 31/4747 (2013.01); A61K 31/519 (2013.01); A61K 31/53 (2013.01); A61K 31/5377 (2013.01); A61K 31/635 (2013.01); A61K 31/675 (2013.01); A61P 35/00 (2018.01); C07D 471/10 (2013.01); C07D 471/20 (2013.01); C07D 491/20 (2013.01); C07D 491/22 (2013.01); C07D 495/20 (2013.01); C07D 495/22 (2013.01); C07B 2200/05 (2013.01); C07B 2200/13 (2013.01)]

30 Claims

1. A compound of formula (I)

wherein

R¹is F, Cl, Br, OCH₃, OCH₂F, OCHF₂, or OCF₃;

R²is F, CL, CF₃, or CN;

X is (CH₂)_1-2, CHF, CHD, CD₂or CF₂;

Y is (CH₂)_0-2, CHF, CHD, CD₂, O, S, OCH₂or CF₂;

Z is CH₂, CD₂, CHF, CDF, CF₂, CH(OH), CO, CH(CH₃), O, or S,

wherein, when Y is O, OCH₂, or S, then Z is CH₂;

wherein, when Z is O, S, or NCH₃, then Y is (CH₂)_0-2, or CF₂;

wherein, when Z is CH(OH), then Y is CHF or CF₂;

J is CR^J;

wherein R^Jis H, F, Cl, Br, CH₃, CD₃, CF₃, CHF₂, CDF₂, OCH₃or CN;

E is CR^Eor N;

wherein R^Eis H, F, Cl, Br, I, CN, CH₃, CH₂CH₃, CH(CH₃)₂, CD₃, CHD₂, CH₂D, CHF₂, CDF₂, C(CH₃)F₂, C(CD₃)F₂, CF₃, cyclopropyl, OCH₃, OCH₂CH₂OH, OCF₃, SCH₃or SCHF₂; and

G is CH or N;

in free form or in a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers.