US 12,168,012 B2
NLRP3 inflammasome inhibitors
Christopher Farady, Basel (CH); Nina Gommermann, Lörrach (DE); Philipp Janser, Basel (CH); Angela MacKay, Basel (CH); Henri Mattes, Michelbach le Bas (FR); Nikolaus Johannes Stiefl, Lörrach (DE); and Juraj Velcicky, Basel (CH)
Assigned to Novartis AG, Basel (CH)
Appl. No. 17/259,252
Filed by Novartis AG, Basel (CH)
PCT Filed Jul. 23, 2019, PCT No. PCT/IB2019/056278
§ 371(c)(1), (2) Date Jan. 11, 2021,
PCT Pub. No. WO2020/021447, PCT Pub. Date Jan. 30, 2020.
Claims priority of application No. 18185580 (EP), filed on Jul. 25, 2018; and application No. 19175246 (EP), filed on May 17, 2019.
Prior Publication US 2021/0308140 A1, Oct. 7, 2021
Int. Cl. A61K 31/53 (2006.01); A61K 31/616 (2006.01); A61K 45/06 (2006.01); C07D 495/14 (2006.01); C07D 513/14 (2006.01); C07D 515/14 (2006.01)
CPC A61K 31/53 (2013.01) [A61K 31/616 (2013.01); A61K 45/06 (2013.01); C07D 495/14 (2013.01); C07D 513/14 (2013.01); C07D 515/14 (2013.01)] 19 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof wherein:
R1 is H, halo, or methyl;
R2 is ethyl substituted with —OH, C1-C4alkoxy, or with one or more halo groups; or
R2 is C3-C6alkyl optionally substituted with OH, halo or C1-4alkoxy; or
R2 is C3-C6cycloalkyl;
R3 is C2-C8alkyl optionally substituted with 1 to 3 substituents independently selected from —NH2, —NH(C1-C4alkyl), —NHC(O)O(C1-C4alkyl), —NHC(O)(C1-C4alkyl), —OH, C1-C4alkoxy, haloC1-C4alkoxy, halo and C3-C5cycloalkyl which is further optionally substituted with OH or halo; or
R3 is C3-C10cycloalkyl or C3-C5cycloalkyl-CH2, each of which is optionally substituted with 1 to 3 substituents independently selected from —OH, C1-C4alkyl, C3-C6cycloalkyl, halo, —OC(O)(C1-C4alkyl), haloC1-C4alkyl, —C(O)O(C1-C4alkyl), hydroxyC1-C4alkyl, C1-C4alkoxy, haloC1-C4alkoxy, —NH2, —NH(C1-C4alkyl), —CO2H; or
R3 is mono or bicyclic aryl, or a mono or bicyclic heteroaryl, each of which is optionally substituted with 1 to 3 substituents independently selected from —OH, C1-C4alkyl, C3-C6cycloalkyl, halo, —OC(O)(C1-C4alkyl), haloC1-C4alkyl, —C(O)O(C1-C4alkyl), hydroxyC1-C4alkyl, C1-C4alkoxy, haloC1-C4alkoxy, —NH2, —SO2NH2, —SO2NH(C1-C4alkyl), —NHSO2(C1-C4alkyl), —NH(C1-C4alkyl), —C(O)NH2, C(O)C1-C4alkyl, —CO2H; or
R3 is a mono or bicyclic heterocyclyl optionally substituted with 1 to 3 substituents independently selected from —OH, oxo, C3-C6cycloalkyl, halo, —C(O)O—C1-C4alkyl, —C(O)C1-C4alkyl, and C1-C4alkyl which is further optionally substituted with 1 to 4 substituents independently selected from C3-C6cycloalkyl, halo, C1-C4alkoxy, haloC1-C4alkoxy and OH;
X is N or CH.