US 11,753,381 B2
Inhibitors of receptor interacting protein kinase I for the treatment of disease
Richard T. Lewis, Missouri City, TX (US); Matthew Michael Hamilton, Missouri City, TX (US); William J. Ray, Houston, TX (US); Fernando Alvarez, Austin, TX (US); Dana E. Pfaffinger, Houston, 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 Sep. 25, 2020, as Appl. No. 17/33,104.
Claims priority of provisional application 62/907,146, filed on Sep. 27, 2019.
Prior Publication US 2021/0094921 A1, Apr. 1, 2021
Int. Cl. C07D 231/06 (2006.01); A61K 31/4965 (2006.01); A61K 31/415 (2006.01); A61K 31/416 (2006.01); C07D 231/56 (2006.01); C07D 403/12 (2006.01); A61K 31/506 (2006.01); A61K 31/5377 (2006.01); C07D 401/14 (2006.01); A61K 31/4439 (2006.01); C07D 471/04 (2006.01); A61K 31/437 (2006.01); C07D 403/08 (2006.01); A61K 31/4155 (2006.01); C07D 413/08 (2006.01); A61K 31/4245 (2006.01); A61K 31/4184 (2006.01); C07D 207/10 (2006.01); A61K 31/40 (2006.01); A61K 31/4015 (2006.01); C07D 401/12 (2006.01); C07D 403/14 (2006.01); A61K 31/497 (2006.01); A61K 31/4192 (2006.01); C07D 487/04 (2006.01); A61K 31/4985 (2006.01); C07D 417/14 (2006.01); A61K 31/427 (2006.01); C07D 241/24 (2006.01); A61K 45/06 (2006.01)
CPC C07D 231/06 (2013.01) [A61K 31/40 (2013.01); A61K 31/4015 (2013.01); A61K 31/415 (2013.01); A61K 31/416 (2013.01); A61K 31/4155 (2013.01); A61K 31/4184 (2013.01); A61K 31/4192 (2013.01); A61K 31/427 (2013.01); A61K 31/4245 (2013.01); A61K 31/437 (2013.01); A61K 31/4439 (2013.01); A61K 31/497 (2013.01); A61K 31/4965 (2013.01); A61K 31/4985 (2013.01); A61K 31/506 (2013.01); A61K 31/5377 (2013.01); A61K 45/06 (2013.01); C07D 207/10 (2013.01); C07D 231/56 (2013.01); C07D 241/24 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/08 (2013.01); C07D 403/12 (2013.01); C07D 403/14 (2013.01); C07D 413/08 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01)] 8 Claims
 
1. A compound of structural Formula I:

OG Complex Work Unit Chemistry
or a salt thereof, wherein:
X is alkylene and is optionally substituted with one or more R7,
or X is chosen from carbamoyl, carbonyl, and a bond;
R1a and R1b, together with the intervening nitrogen, combine to form a pyrazoline, which is optionally substituted with one R3, and which is optionally substituted with one or more R4;
R2 is chosen from hydrogen, hydroxy, cyano, and halo,
or R2 is chosen from alkyl, amino, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, (cycloalkyl)oxy, (heterocycloalkyl)oxy, (aryl)oxy, (heteroaryl)oxy, (alkyl)carbonyl, (cycloalkyl)carbonyl, (heterocycloalkyl)carbonyl, (aryl)carbonyl, (alkyl)amino, (cycloalkyl)amino, (heterocycloalkyl)amino, (aryl)amino, and (heteroaryl)amino, any of which is optionally substituted with one or more R5;
R3 is chosen from aryl, (aryl)oxy, heteroaryl, (heteroaryl)oxy, cycloalkyl, and heterocycloalkyl, any of which is optionally substituted with one or more R6;
each R4 is independently chosen from alkyl, halo, cyano, and hydroxy;
each R5 is independently chosen from halo, cyano, amido, alkyl, alkoxy, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, haloalkyl, oxo, P(O)(CH3)2, SO2CH3, aryl optionally substituted with one or more alkyl, and heteroaryl optionally substituted with one or more alkyl;
two R5, together with the intervening atoms, optionally combine to form a cycloalkyl or heterocycloalkyl;
each R6 is independently chosen from halo, alkyl, cycloalkyl, cyano, alkoxy, hydroxy, haloalkyl, hydroxyalkyl, and haloalkoxy; and
each R7 is independently chosen from alkyl, cyano, halo, and hydroxy.