US 11,702,422 B2
Imidazopyridazines as modulators of IL-17
Steven Goldberg, San Diego, CA (US); Timothy B. Rhorer, San Diego, CA (US); Connor Martin, San Diego, CA (US); Steven P. Meduna, San Diego, CA (US); Stefan McCarver, San Diego, CA (US); Alexander Valdes, San Diego, CA (US); Douglas Behenna, San Juan Capistrano, CA (US); Xiaohua Xue, San Diego, CA (US); and John Keith, San Diego, CA (US)
Assigned to JANSSEN PHARMACEUTICA NV, Beerse (BE)
Filed by Janssen Pharmaceutica NV, Beerse (BE)
Filed on Jan. 14, 2022, as Appl. No. 17/576,535.
Application 17/576,535 is a continuation of application No. 17/242,512, filed on Apr. 28, 2021.
Claims priority of provisional application 63/017,682, filed on Apr. 30, 2020.
Prior Publication US 2023/0081548 A1, Mar. 16, 2023
Int. Cl. C07D 487/04 (2006.01)
CPC C07D 487/04 (2013.01) 24 Claims
 
1. A compound of Formula I′:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R1 is —C(1-6)alkyl, —C(0-2)alkylC(3-8)cycloalkyl, —C(0-2)alkyl-cyclopropyl-C(1-3)perfluoroalkyl, or a 5- to 6-membered heterocyclyl having 1 to 2 nitrogen atoms;
wherein the —C(1-6)alkyl is unsubstituted or substituted with one to six R1a groups;
wherein the —C(0-2)alkylC(3-8)cycloalkyl is unsubstituted or substituted with one to six R1b groups; and
wherein the 5- to 6-membered heterocyclyl is unsubstituted or substituted with one to three R1c groups;
R2 is H, —C(3-5)cycloalkyl, —C(1-4)alkyl, or a 6-membered heterocycle having 1 to 2 oxygen atoms; wherein the —C(1-4)alkyl is unsubstituted or substituted with one to six R2a groups; and wherein the —C(3-5)cycloalkyl is unsubstituted or substituted with —CN;
R1a, R1b and R2a are each independently fluorine, —C(3-5)cycloalkyl, —CN, —OH, —OC(1-3)alkyl or —OC(3-4)cycloalkyl, wherein the —OC(1-3)alkyl and —OC(3-4)cycloalkyl groups are unsubstituted or substituted with one to three fluorine atoms;
each R1c is independently —OCH3, —OCF3, —OCHF2, or —C(1-4)alkyl that is unsubstituted or substituted with one to six fluorine atoms;
R3 is —C(0-1)alkylC(3-6)cycloalkyl, —C(3-6)alkyl or —C(1-2)alkyl-O—C(1-3)alkyl, wherein the —C(0-1)alkylC(3-6)cycloalkyl, —C(3-6)alkyl and —C(1-2)alkyl-O—C(1-3)alkyl are unsubstituted or substituted with one to five R3a groups each independently selected from fluorine, —CH3—CHF2, —CF3, OH and ═O;
R4 is —C(3-6)cycloalkyl or phenyl;
wherein the C(3-8)cycloalkyl is unsubstituted or substituted with one to three R4a groups each independently selected from halogen, —OC(1-3)alkyl, and —C(1-4)alkyl wherein the —OC(1-3)alkyl, and —C(1-4)alkyl are unsubstituted or substituted with one to three fluorine atoms;
alternatively, two R4a groups attached to the same ring atom can be combined with the atom to which they are attached to form a C(3-8)cycloalkyl;
wherein the phenyl is unsubstituted or substituted with one to three R4b groups each independently selected from halogen, —CN, —C(0-2)alkyl-C(3-4)cycloalkyl, —OC(0-2)alkyl-C(3-4)cycloalkyl, —OC(1-3)alkyl, —C(1-4)alkyl and a 3 to 6-membered heterocyclyl having 1 to 2 heteroatoms selected from N and O, wherein the —OC(1-3)alkyl, —C(0-2)alkyl-C(3-4)cycloalkyl and —C(1-4)alkyl are unsubstituted or substituted with one to three fluorine atoms, and wherein the heterocyclyl is unsubstituted or substituted with 1 oxo; and
R5 is hydrogen or halogen.