US 11,912,668 B2
GCN2 and perk kinase inhibitors and methods of use thereof
Daniel L. Flynn, Waltham, MA (US); Patrick Kearney, Waltham, MA (US); Jeffery Zwicker, Waltham, MA (US); Gada Al-Ani, Waltham, MA (US); Salim Javed, Waltham, MA (US); Yu Mi Ahn, Waltham, MA (US); Kristen Stoltz, Waltham, MA (US); and Bertrand Le Bourdonnec, Waltham, MA (US)
Assigned to Deciphera Pharmaceuticals, LLC, Waltham, MA (US)
Filed by Deciphera Pharmaceuticals, LLC, Waltham, MA (US)
Filed on Nov. 17, 2021, as Appl. No. 17/528,478.
Claims priority of provisional application 63/185,846, filed on May 7, 2021.
Claims priority of provisional application 63/115,496, filed on Nov. 18, 2020.
Prior Publication US 2022/0274934 A1, Sep. 1, 2022
Int. Cl. C07D 471/04 (2006.01); C07D 239/84 (2006.01); A61P 35/00 (2006.01); C07D 401/12 (2006.01)
CPC C07D 239/84 (2013.01) [A61P 35/00 (2018.01); C07D 401/12 (2013.01); C07D 471/04 (2013.01)] 15 Claims
 
1. A compound represented by Formula I-R:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, enantiomer, stereoisomer, or tautomer thereof, wherein:
X1 is selected from the group consisting of CH and N;
X3 is selected from the group consisting of C—O-L2-E2, C-L2-E2, and C—N(R2)-L2-E2
X10 is selected from the group consisting of CR5 and N;
X11 is selected from the group consisting of CR7 and N;
R1 is selected from the group consisting of alkyl, (C═O)R13, cycloalkyl, alkoxyalkyl, cycloalkoxyalkyl, aminoalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, and heteroarylalkyl,
wherein each of aryl and heteroaryl is optionally substituted with one or more occurrences of a substituent independently selected from the group consisting of haloalkyl, alkyl, haloalkoxy, alkoxy, halo, amino, amido, acyl, alkoxyalkyl, hydroxy, hydroxyalkyl, cyano, cyanoalkyl, and heterocyclyl, and
wherein heterocyclyl is optionally substituted with one or more occurrences of a substituent independently selected from the group consisting of alkyl, alkoxy, alkoxyalkyl, amido, amino, aminoalkyl, acyl, haloalkyl, haloalkoxy, halo, hydroxy, hydroxyalkyl, oxo, cyano, cyanoalkyl, and sulfonyl;
R2 is selected from the group consisting of H and alkyl;
R3 is selected from the group consisting of H, alkyl, and halo;
R4 and R5 are each independently selected from the group consisting of halo, H, alkoxy, alkylamino, amino, alkyl, haloalkyl and CN;
R6 is selected from the group consisting of halo, H, and alkyl;
R7 is selected from the group consisting of H and F;
R10 and R11 are each independently selected from the group consisting of hydroxyalkyl, hydroxycycloalkyl, alkoxyalkyl, alkoxycycloalkyl, amino, aminoalkyl, aminocycloalkyl, aminocarbonyl, acylamino, halo, cyano, alkoxy, alkylamino, H, cyanoalkyl, alkyl, cycloalkyl, haloalkyl, cycloalkoxy, cycloalkylamino, heterocyclyl, alkoxycarbonyl, and heterocyclylalkyl;
R13 is selected from the group consisting of H, alkyl, cycloalkyl, alkoxyalkyl, cycloalkoxyalkyl, aminoalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, and heteroarylalkyl,
wherein each of aryl and heteroaryl is optionally substituted with one or more occurrences of a substituent independently selected from the group consisting of haloalkyl, alkyl, haloalkoxy, alkoxy, halo, amino, amido, acyl, alkoxyalkyl, hydroxy, hydroxyalkyl, cyano, cyanoalkyl, and heterocyclyl, and
wherein heterocyclyl is optionally substituted with one or more occurrences of a substituent independently selected from the group consisting of alkyl, alkoxy, alkoxyalkyl, amido, amino, aminoalkyl, acyl, haloalkyl, haloalkoxy, halo, hydroxy, hydroxyalkyl, oxo, cyano, cyanoalkyl, and sulfonyl;
R15 is selected from the group consisting of alkyl, cycloalkyl, and heterocycyl;
L2 is selected from the group consisting of a direct bond and C1-C6alkyl, wherein C1-C6alkyl is optionally substituted with (E21)p;
E2 is selected from the group consisting of hydroxy, alkoxy, alkoxyalkyl, cyano, halo, sulfonyl, H, alkyl, amino, amido, acyl, haloalkoxy, haloalkyl, and heterocyclyl,
wherein heterocyclyl is optionally substituted with one or more occurrences of a substituent independently selected from the group consisting of alkyl, alkoxy, amido, amino, acyl, haloalkyl, haloalkoxy, halo, hydroxy, hydroxyalkyl, oxo, cyano, and cyanoalkyl;
E21, at each occurrence, is independently selected from the group consisting of H, alkyl, cycloalkyl, alkoxy, cyano, cyanoalkyl, haloalkoxy, haloalkyl, hydroxy, hydroxyalkyl, and halo, and
each p is independently 0, 1 or 2.