Methods and compositions for targeting PD-L1

Inventors

Wu, Tongfei • Raboisson, Pierre Jean-Marie Bernard • Gonzalvez, Francois • Stoycheva, Antitsa Dimitrova • Liu, Cheng • Deval, Jerome • McGowan, David

Assignees

Aligos Therapeutics Inc

Abstract

The present disclosure related to compounds that can be useful as inhibitors of PD-1, PD-L1 or the PD-1/PD-L1 interaction. Also disclosed herein are pharmaceutical compositions of that can include a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and uses of or methods of using a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for the treatment of PD-L1 related diseases including but not limited to liver diseases, cancer, hepatocellular carcinoma, viral diseases, or hepatitis B.

Core Innovation

The invention relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, having a defined structural framework with specified selections for X1, X2, X3, Y1 through Y8 and numerous substituent groups including R1a, R1b, R1c, R1d, R1e, R1f, R1g, R2a through R2h, R3a, R4a, R4b, R5a through R5f, and Rm1, Rn1, Rn2, Rx1, Rx2, Ry1, and Ry2. The structural selections define a tightly defined chemical space for the compound of Formula (I).

X2 is O, and X1 and Y1-Y4 and Y6-Y8 are selected from CH and N-type alternatives as set out. The substituent variables are limited to enumerated groups such as hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, and various heterocyclic substituents described as monocyclic and fused-heterocyclyl groups, with further optional substitution patterns defined for those ring systems.

The disclosure includes PD-1/PD-L1 pathway targeting compounds, including inhibitors of PD-1, PD-L1, or the PD-1/PD-L1 interaction, and provides pharmaceutical compositions containing Formula (I) compounds, including pharmaceutically acceptable salts. The document also describes compounds and intermediates within the same Formula (I) space, showing structural variation through halogen substitution, chiral side-chain variants, and protected carboxylate or ester derivatives.

Claims Coverage

The independent claim content identifies a Formula (I) compound with extensive, explicitly defined substituent options and optional pharmaceutical salt formation. The claim coverage also includes a method of treating hepatocellular carcinoma (HCC), and the broader disclosure includes PD-1/PD-L1 pathway targeting compounds.

The claim coverage is directed to Formula (I) compounds with pharmaceutically acceptable salts and a large but explicitly constrained substituent space defined through enumerated structural alternatives for multiple atom and substituent positions. It also includes treatment of hepatocellular carcinoma by administering the claimed compound or salt, and the broader disclosure includes PD-1/PD-L1 pathway targeting compounds.

Stated Advantages

Documented Applications