US 12,234,230 B2
Substituted benzyl-triazole compounds for Cbl-b inhibition, and further uses thereof
Arthur T. Sands, San Francisco, CA (US); Neil F. Bence, San Francisco, CA (US); Christoph W. Zapf, San Francisco, CA (US); Frederick Cohen, San Francisco, CA (US); Chenbo Wang, San Francisco, CA (US); Thomas Cummins, San Francisco, CA (US); Hiroko Tanaka, San Francisco, CA (US); Hunter Shunatona, Oakland, CA (US); Mario Cardozo, San Francisco, CA (US); Dahlia Weiss, San Mateo, CA (US); and Jennifa Gosling, San Francisco, CA (US)
Assigned to NURIX THERAPEUTICS, INC., San Francisco, CA (US)
Filed by Nurix Therapeutics, Inc., San Francisco, CA (US)
Filed on Jun. 29, 2022, as Appl. No. 17/853,904.
Application 17/853,904 is a division of application No. 16/913,949, filed on Jun. 26, 2020, granted, now 11,401,267.
Claims priority of provisional application 62/888,845, filed on Aug. 19, 2019.
Claims priority of provisional application 62/888,870, filed on Aug. 19, 2019.
Claims priority of provisional application 62/880,285, filed on Jul. 30, 2019.
Claims priority of provisional application 62/866,914, filed on Jun. 26, 2019.
Prior Publication US 2023/0150991 A1, May 18, 2023
Int. Cl. C07D 413/14 (2006.01); C07D 401/14 (2006.01); C07D 403/10 (2006.01); C07D 403/12 (2006.01); C07D 405/14 (2006.01); C07D 471/04 (2006.01)
CPC C07D 413/14 (2013.01) [C07D 401/14 (2013.01); C07D 403/10 (2013.01); C07D 403/12 (2013.01); C07D 405/14 (2013.01); C07D 471/04 (2013.01)] 5 Claims
 
1. A method of producing a modified immune cell, comprising culturing a cell population containing an immune cell in the presence of an effective amount of a Cbl-b inhibitor to modulate activity of the immune cell, thereby producing the modified immune cell, wherein the Cbl-b inhibitor is a compound of Formula (I)

OG Complex Work Unit Chemistry
or a tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein

OG Complex Work Unit Chemistry
Z1 is CH or nitrogen;
Z2 is CH or nitrogen;
R1 is —CF3 or cyclopropyl;
R2 is —CF3 or cyclopropyl;
R3 is hydrogen, C1-C2 alkyl, or C1-C2 haloalkyl;
R4 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, 4- to 8-membered heterocyclyl, or C3-C6 cycloalkyl,
wherein the heterocyclyl or cycloalkyl groups are optionally substituted by one to five R6 groups;
or R3 and R4 are taken together with the carbon atom to which they are attached to form a C3-C5 cycloalkyl or 4- to 6-membered heterocyclyl, each of which is optionally substituted by one to five R6 groups;
R5 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl;
each R6 is independently C1-C6 alkyl, halo, hydroxy, —O(C1-C6 alkyl), —CN,
C1-C6 alkyl-CN, C1-C6 alkyl-OH, or C1-C6 haloalkyl;
or two R6 groups attached to the same carbon atom are taken together with the carbon atom to which they are attached to form a spiro C3-C6 cycloalkyl or spiro 4- to 6-membered heterocyclyl;
X is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-OH, C1-C6 alkyl-CN,
C3-C6 cycloalkyl optionally substituted by one to five R8 groups, or

OG Complex Work Unit Chemistry
is 4- to 7-membered heterocyclyl or 5- to 8-membered heteroaryl, wherein each heterocyclyl or heteroaryl optionally contains one to two additional heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and wherein each heterocyclyl or heteroaryl is optionally substituted by one to five R8 groups;
each R7 is independently hydrogen, C1-C6 alkyl, C1-C6 alkyl-OH, or C1-C6 haloalkyl;
or two R7 groups are taken together with the carbon atom to which they are attached to form a C3-C5 cycloalkyl or 3- to 5-membered heterocyclyl; and
each R8 is independently halo, C1-C6 alkyl, C1-C6 alkyl-CN, C1-C6 alkyl-OH,
C1-C6 haloalkyl, —CN, oxo, or —O(C1-C6 alkyl);
or two R8 groups are taken together with the carbon atom or atoms to which they are attached to form a spiro or fused C3-C5 cycloalkyl or 3- to 5-membered heterocyclyl.