US 11,655,243 B2
Pyridine and pyrazine derivatives as preferential cannabinoid 2 agonists
Simon M. Ametamey, Zurich (CH); Kenneth Atz, Basel (CH); Luca Gobbi, Basel (CH); Uwe Grether, Basel (CH); Wolfgang Guba, Basel (CH); and Julian Kretz, Basel (CH)
Assigned to HOFFMANN-LA ROCHE INC., Little Falls, NJ (US); and EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH, Zurich (CH)
Filed by HOFFMANN-LA ROCHE INC., Little Falls, NJ (US); and EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH, Zurich (CH)
Filed on Dec. 17, 2020, as Appl. No. 17/125,647.
Application 17/125,647 is a continuation of application No. PCT/EP2019/066733, filed on Jun. 25, 2019.
Claims priority of application No. 18180114 (EP), filed on Jun. 27, 2018.
Prior Publication US 2021/0115027 A1, Apr. 22, 2021
Int. Cl. C07D 401/04 (2006.01); C07D 403/04 (2006.01); A61K 31/497 (2006.01); C07D 405/14 (2006.01); A61K 9/08 (2006.01); A61K 9/20 (2006.01); A61K 9/28 (2006.01); A61K 9/48 (2006.01); A61K 47/12 (2006.01); A61K 47/34 (2017.01)
CPC C07D 405/14 (2013.01) [A61K 9/08 (2013.01); A61K 9/2013 (2013.01); A61K 9/2018 (2013.01); A61K 9/2027 (2013.01); A61K 9/2054 (2013.01); A61K 9/2059 (2013.01); A61K 9/2813 (2013.01); A61K 9/2853 (2013.01); A61K 9/2866 (2013.01); A61K 9/485 (2013.01); A61K 9/4858 (2013.01); A61K 9/4866 (2013.01); A61K 47/12 (2013.01); A61K 47/34 (2013.01); C07D 401/04 (2013.01); C07B 2200/05 (2013.01)] 16 Claims
 
1. A compound of formula (I)

OG Complex Work Unit Chemistry
wherein
A1 is —CH— or nitrogen;
A2 is —CH2— or carbonyl;
R1 is haloalkoxyalkylcycloalkyl, haloalkylcycloalkyl, haloalkoxyalkyl, hydroxyalkylcycloalkyl, oxetanyl, haloalkoxyalkyloxetanyl, hydroxyalkyloxetanyl, haloalkyloxetanyl, 1-fluoroethyl, 1-fluoro-prop-2-yl, fluoro-tert.-butyl, cyclopropylfluoromethyl, fluorocyclopropyl, halooxanyl, halotetrahydrofuranyl, phenylalkoxyalkylcycloalkyl, 1-fluoro-1,1-dideuteroprop-2-yl, fluorodideuteromethyl, fluorodideuteromethyloxyalkylcycloalkyl, 2-fluoro-2,2-dideuteroethyloxyalkylcycloalkyl, fluorodideuteromethylcycloalkyl, fluorodideuteromethyloxyalkyl, fluorodideuteromethylalkyl, fluorodideuteromethyloxyalkyloxetanyl, 2-fluoro-2,2-dideuteroethyloxyalkyloxetanyl, 3-fluoro-3,3-dideuteropropyloxyalkyloxetanyl or fluorodideuteromethyloxetanyl;
R2 is alkoxyazetidinyl, haloazetidinyl, dihaloazetidinyl, pyrrolidinyl or alkylphenylsulfonyloxyazetidinyl;
R3 and R4 are independently selected from hydrogen, alkyl, alkenyl and deuterioalkyl;
R5 is hydrogen, alkyl, haloalkyl, deuterioalkyl, alkylphenylsulfonyloxyalkyl, alkylphenylsulfonyloxydeuterioalkyl or hydroxyalkyl; and
X is oxygen or —NH—;
or a pharmaceutically acceptable salt thereof.