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Synthesis and Evaluation of Biphenyl-1,2,3-Triazol-Benzonitrile Derivatives as PD-1/PD-L1 Inhibitors.

ABSTRACT: In this study, we designed and synthesized a series of 3-(4-((5-((2-methylbiphenyl-3-yl) methoxy)-2-(piperazin-1-ylmethyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives and examined the effect of the compounds on the interaction between PD-1 and PD-L1. Among the newly synthesized compounds, compound 7 exhibited the most potent inhibitory activity for PD-1/PD-L1 binding, with an IC50 value being 8.52 ?M, through homogeneous time-resolved fluorescence (HTRF) assay. Docking studies indicated that compound 7 can very well interact with PD-L1 dimerization like BMS-202 as a positive control, consistent with the results of the HTRF assay. Compound 7 is thus a promising candidate for further optimization as an inhibitor of the PD-1/PD-L1 signaling pathway.

SUBMITTER: Narva S

PROVIDER: S-EPMC7450630 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Synthesis and Evaluation of Biphenyl-1,2,3-Triazol-Benzonitrile Derivatives as PD-1/PD-L1 Inhibitors.

Narva Suresh S Xiong Xuqiong X Ma Xudong X Tanaka Yoshimasa Y Wu Yanling Y Zhang Wen W

ACS omega 20200814 33

In this study, we designed and synthesized a series of 3-(4-((5-((2-methylbiphenyl-3-yl) methoxy)-2-(piperazin-1-ylmethyl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)benzonitrile derivatives and examined the effect of the compounds on the interaction between PD-1 and PD-L1. Among the newly synthesized compounds, compound 7 exhibited the most potent inhibitory activity for PD-1/PD-L1 binding, with an IC50 value being 8.52 μM, through homogeneous time-resolved fluorescence (HTRF ...[more]

PMID: 32875254

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