Development and Synthesis of DNA-Encoded Benzimidazole Library

被引：37

作者：

Ding, Yun ^{[1
]}

Chai, Jing ^{[1
]}

Centrella, Paolo A. ^{[1
,2
]}

Gondo, Chenaimwoyo ^{[1
,3
]}

DeLorey, Jennifer L. ^{[1
,4
]}

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

机构：

[1] GlaxoSmithKline, Platform Technol & Sci, 200 Cambridgepk Dr, Cambridge, MA 02140 USA

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

[3] McKinsey & Co Inc, 1 Jermyn St, London SW1Y 4UH, England

[4] Tedor Pharma Inc, 400 Highland Corp Dr, Cumberland, MD 02864 USA

来源：

ACS COMBINATORIAL SCIENCE | 2018年 / 20卷 / 05期

关键词：

benzimidazole; DNA-encoded library technology; COMBINATORIAL CHEMISTRY; DISCOVERY; INHIBITORS; SELECTION; ANTAGONISTS; TECHNOLOGY; SCAFFOLD; LIGANDS; DESIGN;

D O I：

10.1021/acscombsci.8b00009

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Encoded library technology (ELT) is an effective approach to the discovery of novel small-molecule ligands for biological targets. A key factor for the success of the technology is the chemical diversity of the libraries. Here we report the development of DNA-conjugated benzimidazoles. Using 4-fluoro-3-nitrobenzoic acid as a key synthon, we synthesized a 320 million-member DNA-encoded benzimidazole library using Fmoc-protected amino acids, amines and aldehydes as diversity elements. Affinity selection of the library led to the discovery of a novel, potent and specific antagonist of the NK3 receptor.

引用

页码：251 / 255

页数：5

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