US 12,421,242 B2
Substituted tetrahydropyrrolo-pyridinone compounds and their use in treating medical conditions
Kevin Matthew Gardinier, Arlington, MA (US); James Edmund Audia, Chicago, IL (US); James Monn, Indianapolis, IN (US); Jason Myers, Indianapolis, IN (US); Nadia M. Ahmad, Saffron Walden (GB); Emanuela Gancia, Saffron Walden (GB); Niall Wagstaff, Saffron Walden (GB); David G. Evans, Saffron Walden (GB); Fabien Jean Ghislain Roussel, Saffron Walden (GB); and Elizabeth Anne Skidmore, Saffron Walden (GB)
Assigned to Karuna Therapeutics, Inc., Princeton, NJ (US)
Filed by Karuna Therapeutics, Inc., Princeton, NJ (US)
Filed on Jun. 11, 2024, as Appl. No. 18/740,233.
Application 18/740,233 is a continuation of application No. PCT/US2023/084185, filed on Dec. 15, 2023.
Claims priority of provisional application 63/433,156, filed on Dec. 16, 2022.
Prior Publication US 2024/0336619 A1, Oct. 10, 2024
Int. Cl. C07D 487/04 (2006.01); A61K 31/437 (2006.01); A61K 31/444 (2006.01); C07D 519/00 (2006.01)
CPC C07D 487/04 (2013.01) [A61K 31/437 (2013.01); A61K 31/444 (2013.01); C07D 519/00 (2013.01)] 50 Claims
 
1. A compound represented by Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof;
wherein:
R1 is C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl,-(C1-6 alkylene)-(C3-6 cycloalkyl), or hydrogen;
R2 is halo, C1-4 alkyl, C1-4 haloalkyl, or hydrogen;
R3 is C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxyl,-S-(C1-4 alkyl), or halo;
R4 represents independently for each occurrence C1-4 alkyl, C1-4 haloalkyl, or halo;
R5 represents independently for each occurrence C1-6 alkyl, halo, C1-6 haloalkyl, C3-6 cycloalkyl, hydroxyl, C1-6 alkoxyl,-(C1-6 alkylene)-(C1-6 alkoxyl),-(C1-6 alkylene)-(C3-6 cycloalkyl),-(C1-6 haloalkylene)-(C3-6 cycloalkyl), or —(C1-6 alkylene)-(C3-6 halocycloalkyl); or two occurrences of R5 are taken together with their intervening atoms to form a 4-7 membered ring containing 1 or 2 heteroatoms independently selected from the group consisting of oxygen, nitrogen, and sulfur;
R6 is (i) —(C0-4 alkylene)-(3-7 membered saturated or unsaturated heterocyclyl containing 1, 2, or 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur), (ii)-(C0-4 alkylene)-(5-6 membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur), or (iii)-(C0-4 alkylene)-phenyl, wherein the heterocyclyl, heteroaryl, and phenyl are substituted with 0, 1, 2, or 3 occurrences of R7,
R7 represents independently for each occurrence C1-6 alkyl, halo, C1-6 haloalkyl, C3-6 cycloalkyl, hydroxyl, or C1-6 alkoxyl;
A1 is a 5-6 membered monocyclic heteroaryl containing 1, 2, or 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic heteroaryl containing 1, 2, or 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, or phenyl, wherein the monocyclic heteroaryl, bicyclic heteroaryl, and phenyl are substituted with n occurrences of R5 and t occurrences of R6;
m is 0, 1, 2, or 3;
n is 0, 1, or 2; and
t is 0 or 1.