Synthesis and evaluation of triazole-containing aryl/acyloxy prodrugs of a BTN3A1 ligand.

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Tác giả: Chia-Hung Christine Hsiao, Parker A Kintigh, Girija Pawge, Sarita Rani, Joseph P Sarno, Umed Singh, Andrew J Wiemer, David F Wiemer

Ngôn ngữ: eng

Ký hiệu phân loại: 785.13 *Trios

Thông tin xuất bản: France : European journal of medicinal chemistry , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 497646

The most effective natural ligand for the butyrophilins is (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate. However, due to its susceptibility to plasma hydrolysis and its high charge that limits passive diffusion across cell membranes, its potential as a drug is limited. Our efforts to identify compounds that stimulate γδ T cell proliferation have been focused on phosphonates to gain metabolic stability and phosphonate prodrugs to improve diffusion into cells. To identify potential prodrugs that are soluble, relatively stable in plasma, and undergo facile hydrolysis once inside the cell, we have prepared a series of aryl acyloxyesters where the acyl group includes a triazole moiety. Several of these novel prodrug forms have been shown to demonstrate nanomolar potency for T cell activation and relatively long half-lives in plasma. Interestingly, compound 26b stimulated T cells at sub-nanomolar levels (proliferation EC
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