US 11,944,606 B2
Azaindoles as inhibitors of HPK1
Timothy Heffron, Burlingame, CA (US); Sushant Malhotra, Burlingame, CA (US); BinQing Wei, Belmont, CA (US); Bryan Chan, Foster City, CA (US); Lewis Gazzard, Belmont, CA (US); Emanuela Gancia, Harlow (GB); Michael Lainchbury, Harlow (GB); Andrew Madin, Harlow (GB); Eileen Seward, Harlow (GB); and Yonghan Hu, Shanghai (CN)
Assigned to Genentech, Inc., South San Francisco, CA (US)
Filed by Genentech, Inc., South San Francisco, CA (US)
Filed on Feb. 17, 2021, as Appl. No. 17/178,021.
Application 17/178,021 is a division of application No. 16/568,459, filed on Sep. 12, 2019, granted, now 10,952,995.
Application 16/568,459 is a continuation of application No. PCT/EP2018/056390, filed on Mar. 14, 2018.
Claims priority of application No. PCT/CN2017/076713 (WO), filed on Mar. 15, 2017.
Prior Publication US 2021/0299110 A1, Sep. 30, 2021
Int. Cl. A61K 31/437 (2006.01); A61K 31/444 (2006.01); A61K 31/506 (2006.01); A61K 31/513 (2006.01); A61K 31/5377 (2006.01); C07D 471/04 (2006.01)
CPC A61K 31/437 (2013.01) [A61K 31/444 (2013.01); A61K 31/506 (2013.01); A61K 31/513 (2013.01); A61K 31/5377 (2013.01); C07D 471/04 (2013.01)] 20 Claims
 
1. A method for inhibiting HPK1 comprising contacting HPK1 with an effective amount of a compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein,
G1 is N or C—Rx1;
G2 is N or C—Rx2;
G3 is N or C—Rx3;
G4 is N or C—Rx4;
wherein, 0, 1 or 2 of G1, G2, G3, and G4 is N;
Rx1, Rx2, Rx3 and Rx4, if present, in each instance, is independently selected from the group consisting of hydrogen, halo, C6-C20 aryl optionally substituted with one or two R1a, C1-C20 heteroaryl optionally substituted with one or two R1a, —CONR6R7, —NR6R7, and —N(R8)—CO(R9), provided that at least one of Rx1, Rx2, Rx3 and Rx4 is other than hydrogen;
wherein, R6 and R7 taken together with the N to which each is bound form a 4-, 5-, 6- or 7-member cyclic or heterocyclic ring, wherein said heterocyclic ring may contain one or two additional heteroatoms selected from the group consisting of N, S and O, said ring may be optionally substituted with one or two R1a; or
R6 and R7 are independently hydrogen or alkyl;
wherein, R8 and R9 taken together with the N or the carbonyl to which each is bound form a 4-, 5-, 6- or 7-member cyclic or heterocyclic ring, wherein said heterocyclic ring may contain one or two additional heteroatoms selected from the group consisting of N, S and O, said ring may be optionally substituted with one or two R1a; or
R8 and R9 are independently hydrogen or alkyl;
wherein, in each instance, R1a is independently taken together with the carbon to which it is bound to form a carbonyl; or R1a is hydrogen, alkyl, hydroxyl, hydroxyalkyl, halo or haloalkyl;
R1 is hydrogen, alkyl, hydroxyl, hydroxyalkyl, halo or haloalkyl;
R2 is alkyl, alkoxy, halo, haloalkyl-, haloalkoxy-, —R5—O—R5, —SO2R5, —SOR5, or cycloalkyl; and
R3 and R4, in each instance, is independently hydrogen, alkyl, alkoxy, halo, haloalkyl-, haloalkoxy-, —R5—O—R5, —SO2R5, —SOR5, or cycloalkyl;
wherein R5, in each instance, is independently an unsubstituted alkyl; provided that R1 and R4 are not both hydrogen.