US 12,419,885 B2
Kinase inhibitors and methods of use thereof
Florence Fevrier Wagner, Cambridge, MA (US); Jennifer Q. Pan, Cambridge, MA (US); Sivaraman Dandapani, Cambridge, MA (US); Andrew Germain, Cambridge, MA (US); Edward Holson, Cambridge, MA (US); Benito Munoz, Cambridge, MA (US); Partha P. Nag, Cambridge, MA (US); Michael C. Lewis, Cambridge, MA (US); Stephen J. Haggarty, Gloucester, MA (US); Joshua A. Bishop, Cambridge, MA (US); Kimberly Stegmaier, Jamaica Plain, MA (US); Michel Weiwer, Cambridge, MA (US); and Versha Banerji, Winnipeg (CA)
Assigned to The Broad Institute, Inc., Cambridge, MA (US); Dana-Farber Cancer Institute, Inc., Boston, MA (US); and The General Hospital Corporation, Boston, MA (US)
Filed by The Broad Institute, Inc., Cambridge, MA (US); Dana-Farber Cancer Institute, Inc., Boston, MA (US); and The General Hospital Corporation, Boston, MA (US)
Filed on Jun. 10, 2021, as Appl. No. 17/344,830.
Application 17/344,830 is a continuation of application No. 16/198,589, filed on Nov. 21, 2018, granted, now 11,052,080.
Application 16/198,589 is a continuation of application No. 14/799,281, filed on Jul. 14, 2015, granted, now 10,137,122.
Application 14/799,281 is a continuation of application No. 14/052,661, filed on Oct. 11, 2013, granted, now 9,096,594.
Claims priority of provisional application 61/779,394, filed on Mar. 13, 2013.
Claims priority of provisional application 61/713,314, filed on Oct. 12, 2012.
Prior Publication US 2022/0160702 A1, May 26, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/4745 (2006.01); A61K 31/4747 (2006.01); C07D 471/04 (2006.01); C07D 471/10 (2006.01)
CPC A61K 31/4745 (2013.01) [A61K 31/4747 (2013.01); C07D 471/04 (2013.01); C07D 471/10 (2013.01)] 42 Claims
 
1. A method of treating a GSK3- or CK1-mediated disorder comprising administering to a subject suffering from a GSK3- or CK1-mediated disorder an effective amount of a compound of formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein:
the GSK3- or CK1-mediated disorder is a neurological disease, psychiatric disorder, cancer, or metabolic disorder;
R1 is selected from the group consisting of optionally substituted C1-6 alkyl, optionally substituted phenyl, and optionally substituted heteroaryl;
R2 is optionally substituted C1-6 alkyl;
or R1 and R2 are taken together with their intervening atoms to form an optionally substituted, 3- to 7-membered, monocyclic, saturated, carbocyclyl or heterocyclyl, wherein the carbocyclyl or heterocyclyl formed by taking together R1 and R2 is optionally fused to optionally substituted phenyl or optionally substituted heteroaryl;
R3 is selected from the group consisting of hydrogen, halogen, —CN, —NO2, optionally substituted C1-6 alkyl, optionally substituted, 3- to 6-membered, monocyclic, cycloalkyl, optionally substituted phenyl; ORA, —N(RB)2, and —SRA;
each RA is independently selected from the group consisting of hydrogen and optionally substituted C1-6 alkyl;
each RB is independently selected from the group consisting of hydrogen and optionally substituted C1-6 alkyl;
R4a and R4b are each independently selected from the group consisting of hydrogen, halogen, and optionally substituted C1-6 alkyl;
R5a and R5b are each independently selected from the group consisting of hydrogen, halogen, —CN, —ORA, —N(RB)2, and optionally substituted C1-6 alkyl, or R5a and R5b are taken together with their intervening atoms to form unsubstituted, 3- to 7-membered, monocyclic, saturated, carbocyclyl or heterocyclyl;
R6a and R6b are each independently selected from the group consisting of hydrogen, halogen, and optionally substituted C1-6 alkyl;
each instance of the heteroaryl is independently 5- or 6-membered, monocyclic heteroaryl comprising 1 to 4 ring heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, as valency allows; and
each instance of the heterocyclyl independently comprises 1 to 4 ring heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, as valency allows.