US 11,787,780 B2
Quaternary indazole glucocorticoid receptor antagonists
Hazel Hunt, Storrington (GB); Lorna Duffy, Nottingham (GB); Ian Strutt, Nottingham (GB); Morgan Jouanneau, Nottingham (GB); Thomas Hornsby, Nottingham (GB); Mark Mills, Nottingham (GB); Andrew William Phillips, Nottingham (GB); and Jon-Paul Ward, Nottingham (GB)
Assigned to Corcept Therapeutics Incorporated, Menlo Park, CA (US)
Filed by CORCEPT THERAPEUTICS INCORPORATED, Menlo Park, CA (US)
Filed on Jun. 21, 2021, as Appl. No. 17/353,567.
Claims priority of provisional application 63/042,188, filed on Jun. 22, 2020.
Prior Publication US 2023/0032612 A1, Feb. 2, 2023
Int. Cl. C07D 401/14 (2006.01); C07D 403/04 (2006.01); C07D 403/12 (2006.01); C07D 403/14 (2006.01); C07D 231/56 (2006.01); C07D 409/14 (2006.01); C07D 413/14 (2006.01); C07D 487/04 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 231/56 (2013.01); C07D 403/04 (2013.01); C07D 403/12 (2013.01); C07D 403/14 (2013.01); C07D 409/14 (2013.01); C07D 413/14 (2013.01); C07D 487/04 (2013.01)] 28 Claims
 
1. A compound having the structure of Formula IVa:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
R1 is heterocycloalkyl having 5 to 6 ring members and 1 to 2 heteroatoms each N, phenyl or a heteroaryl having 5 to 6 ring members and 1 to 2 heteroatoms each N or S, each substituted with 1 to 3 R1a groups;
each R1a is independently hydrogen, C1-3 alkyl, C1-3 deuteroalkyl, C1-3 alkoxy, C1-3 hydroxyalkyl, halogen, C1-3 haloalkyl, oxo, —CN, C3-6 cycloalkyl, or heterocycloalkyl having 3 to 5 ring members and 1 to 2 heteroatoms each N or O;
A1, A2, A3 and A4 are each independently ═CR2— or ═N—;
each R2 is independently hydrogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, hydroxy or —CN;
each R3a is independently hydrogen, OH, or oxo;
R3b is C1-6 alkyl, C2-6 alkynyl, C2-6 alkoxyalkyl, C2-6 alkynyl-C3-6 cycloalkyl, C1-6 alkyl-C6-12 aryl, C2-6 alkenyl-C6-12 aryl, C2-6 alkynyl-C6-12 aryl, C1-6 alkyl-O-C6-12 aryl, C1-6 alkoxyalkyl-C6-12 aryl, —C(O)—C6-12 aryl, or C1-6 alkyl-heteroaryl, wherein each heteroaryl has 5 to 10 ring members and 1 to 3 heteroatoms each independently N, O or S, and wherein each aryl and heteroaryl are substituted with 1 to 3 R3b3 groups;
each R3b3 is hydrogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, or C1-6 haloalkoxy;
R4 is C1-6 alkyl, C1-6 haloalkyl, —CN, C3-8 cycloalkyl, 3 to 8 membered heterocycloalkyl having 1 to 3 heteroatoms each independently N, O or S, C6-12 aryl, or 5 to 10 membered heteroaryl having 1 to 5 heteroatoms each independently N, O or S, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each independently substituted with 1 to 5 R4a groups;
each R4a is hydrogen, C1-6 alkyl, C1-6 deuteroalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, —CN, —OH, oxo, —S(O)2R4b, —S(O)2N(R4b)(R4c), C3-6 cycloalkyl, C6-12 aryl, C6-12 aryl, wherein each aryl is optionally substituted with C1-6 alkoxy;
each R4b and R4c is hydrogen or C1-6 alkyl;
L1 is absent; and
L2 is absent, —CH2—, —C(O)—, —C(O)CH2—, —C(O)CH2CH2—, —C(O)CH2O—, —C(O)(CH2)3O—, or —S(O)2.