Design and Synthesis of Biaryl DNA-Encoded Libraries

被引：51

作者：

Ding, Yun ^{[1
]}

Franklin, G. Joseph ^{[1
]}

DeLorey, Jennifer L. ^{[1
,2
]}

Centrella, Paolo A. ^{[1
,3
]}

Mataruse, Sibongile ^{[1
,4
]}

Clark, Matthew A. ^{[1
,3
]}

Skinner, Steven R. ^{[1
]}

Belyanskaya, Svetlana ^{[1
]}

机构：

[1] GlaxoSmithKline, Platform Technol & Sci, ELT Boston, 830 Winter St, Waltham, MA 02451 USA

[2] Tedor Pharma Inc, 400 Highland Corp Dr, Cumberland, RI 02864 USA

[3] X Chem Inc, 100 Beaver St, Waltham, MA 02453 USA

[4] 419 Main St, Wareham, MA 02571 USA

来源：

ACS COMBINATORIAL SCIENCE | 2016年 / 18卷 / 10期

关键词：

Suzuki-Miyaura cross-coupling; DNA-encoded library technology; CHEMICAL LIBRARIES; TECHNOLOGY ELT; DISCOVERY; INHIBITORS; SELECTION; IDENTIFICATION; ANTAGONISTS; CHEMISTRY; POTENT;

D O I：

10.1021/acscombsci.6b00078

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

DNA-encoded library technology (ELT) is a powerful tool for the discovery of new small-molecule ligands to various protein targets. Here we report the design and synthesis of biaryl DNA-encoded libraries based on the scaffold of 5-forrnyl 3-iodobenzoic acid. Three reactions on DNA template, acylation, Suzuki-Miyaura coupling and reductive amination, were applied in the library synthesis. The three cycle library of 3.5 million diversity has delivered potent hits for phosphoinositide 3-kinase alpha (PI3K alpha).

引用

页码：625 / 629

页数：5

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