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US 2021/0276994 A1Published application
Hpk1 inhibitors, preparation method and application thereof
AssigneeZhuhai Yufan Biotechnologies Co., Ltd.
InventorXuebin LIAO
Life of this patent
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Abstract
Disclosed are HPK-1 inhibitors having a structure represented by Formula (X), pharmaceutical compositions comprising the HPK-1 inhibitors, methods of using the HPK-1 inhibitors, such as treating cancers, methods of preparing the HPK-1 inhibitors, and the synthetic intermediates.
Claims46
A compound of Formula X, or a pharmaceutically acceptable salt thereof,
- wherein:
- A is N or CH;
- Ar is an optionally substituted aryl or heteroaryl;
- preferably, an optionally substituted 5 or 6 membered heteroaryl containing 1-4 (1, 2, 3, or 4) ring heteroatoms independently selected from O, S, and N;
- L is a linker of formula J1-J2-J3, wherein each of J1, J2, and J3 is independently null, O, S, SO, SO2, C═O, NH, optionally substituted C1-4 alkylene, provided that L does not contain O—O, O—N, S—S, N—S, O—S, or N—N bond, and at most one of J1, J2, and J3 is SO, SO2, or C═O;
- and
- Cy1 is an optionally substituted aryl or heteroaryl;
- preferably an optionally substituted phenyl or an optionally substituted 5 or 6 membered heteroaryl containing 1-4 (e.g., 1, 2, 3, or 4) ring heteroatoms independently selected from O, S, and N.
5 more elements
A compound selected from Compound A1 to A85, or a pharmaceutically acceptable salt thereof.
A method of identifying a candidate agent for use in combination with a CAR-T cell therapy, the method comprising:
- a) Incubating a test agent and CAR-T cells with a tumor cell, wherein the tumor cell comprises an antigen that can bind to and induce cytotoxicity of the CAR-T cells,
- b) Measuring the cytotoxicity of the CAR-T cells in the presence of the test agent, and optionally
- c) Identifying a candidate agent that enhances the cytotoxicity of the CAR-T cells compared to a control.
Dependencies are inferred from the claim text.