US 11,690,850 B2
Inhibitors of receptor interacting protein kinase I for the treatment of disease
Richard T. Lewis, Missouri City, TX (US); Matthew Hamilton, Missouri City, TX (US); William J. Ray, Houston, TX (US); Fernando Alvarez, Austin, TX (US); Naphtali Reyna, Arlington, TX (US); Jason Cross, Pearland, TX (US); and Suyambu Kesava Vijayan Ramaswamy, Houston, TX (US)
Assigned to Board of Regents, The University of Texas System, Austin, TX (US)
Filed by Board of Regents, The University of Texas System, Austin, TX (US)
Filed on Nov. 19, 2020, as Appl. No. 16/952,422.
Claims priority of provisional application 62/940,428, filed on Nov. 26, 2019.
Prior Publication US 2021/0154204 A1, May 27, 2021
Int. Cl. A61K 31/553 (2006.01); A61K 31/551 (2006.01); C07D 237/24 (2006.01); C07D 401/12 (2006.01); C07D 471/04 (2006.01); C07D 417/12 (2006.01); C07D 403/12 (2006.01); C07D 413/12 (2006.01); C07D 409/12 (2006.01); C07D 498/04 (2006.01); C07D 487/04 (2006.01); C07D 413/14 (2006.01); C07D 401/14 (2006.01); C07D 491/107 (2006.01); A61P 35/00 (2006.01); A61K 31/50 (2006.01); A61K 31/501 (2006.01); A61K 31/506 (2006.01); A61K 31/55 (2006.01); A61K 45/06 (2006.01)
CPC A61K 31/553 (2013.01) [A61K 31/50 (2013.01); A61K 31/501 (2013.01); A61K 31/506 (2013.01); A61K 31/55 (2013.01); A61K 31/551 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07D 237/24 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/12 (2013.01); C07D 409/12 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 417/12 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01); C07D 491/107 (2013.01); C07D 498/04 (2013.01)] 24 Claims
 
1. A compound of structural Formula I:

OG Complex Work Unit Chemistry
or a salt thereof, wherein:
R1 is chosen from alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (cycloalkyl)alkyl, (heterocycloalkyl)alkyl, (aryl)alkyl, and (heteroaryl)alkyl, any one of which is optionally substituted with one or more R5;
R2 is chosen from H, alkyl, haloalkyl, and (alkoxy)alkyl;
R3 is chosen from H, CN, halo, alkyl, and alkoxy;
or R2 and R3, together with the intervening atoms, combine to form a 5-, 6-, or 7-membered cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
R4a is H;
R4b is chosen from

OG Complex Work Unit Chemistry
each R5 is independently chosen from CN, halo, hydroxy, oxo, alkyl, and (alkyl)oxy; and
each R6a is independently chosen from H, CN, halo, hydroxy, oxo, C1-6alkyl, haloC1-6alkyl, C3-7 cycloalkyl, 4- to 11-membered heterocycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, (C2-6alkenyl)C1-6alkyl, (C2-6alkynyl)C1-6alkyl, (C3-7cycloalkyl)C1-6alkyl, (4- to 11-membered heterocycloalkyl)C1-6alkyl, (C6-10aryl)C1-6alkyl, (5- to 10-membered heteroaryl)C1-6 alkyl, (C1-6 alkyl)oxy, (C3-7cycloalkyl)oxy, (4- to 11-membered heterocycloalkyl)oxy, (C6-10aryl)oxy, and (5- to 10-membered heteroaryl)oxy; and
R6b is chosen from H and C1-6alkyl.