A Study in Scaffold Hopping: Discovery and Optimization of Thiazolopyridines as Potent Herbicides That Inhibit Acyl-ACP Thioesterase

被引：10

作者：

Abel, Steven A. G. ^{[1
]}

Alnafta, Neanne ^{[1
]}

Asmus, Elisabeth ^{[1
]}

Bollenbach-Wahl, Birgit ^{[1
]}

Braun, Ralf ^{[1
]}

Dittgen, Jan ^{[1
]}

Endler, Anne ^{[2
]}

Frackenpohl, Jens ^{[1
]}

Freigang, Joerg ^{[3
]}

Gatzweiler, Elmar ^{[1
]}

Heinemann, Ines ^{[1
]}

Helmke, Hendrik ^{[1
]}

Laber, Bernd ^{[1
]}

Lange, Gudrun ^{[1
]}

Machettira, Anu ^{[1
]}

Mcarthur, Gillian ^{[1
]}

Mueller, Thomas ^{[1
]}

Odaybat, Magdalena ^{[1
]}

Reingruber, Anna M. ^{[1
]}

Roth, Sina ^{[1
]}

Rosinger, Christopher H. ^{[1
]}

Schmutzler, Dirk ^{[1
]}

Schulte, Wolfgang ^{[1
]}

Stoppel, Rhea ^{[1
]}

Tiebes, Joerg ^{[1
]}

Volpin, Giulio ^{[4
]}

Barber, David M. ^{[1
]}

机构：

[1] Bayer AG, Crop Sci Div, Res & Dev, Weed Control Res, Ind Pk Hochst, D-65926 Frankfurt, Germany

[2] Targenomix GmbH, D-14476 Potsdam, Germany

[3] Bayer AG, Crop Sci Div, Res & Dev, Hit Discovery, D-40789 Monheim, Germany

[4] Bayer AG, Crop Sci Div, Res & Dev, Small Mol Technol, Ind Pk Hochst, D-65926 Frankfurt, Germany

来源：

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY | 2023年 / 71卷 / 47期

关键词：

acyl-ACP thioesterase; crop protection; herbicides; scaffold hopping; thiazolopyridines;

D O I：

10.1021/acs.jafc.3c02490

中图分类号：

S [农业科学];

学科分类号：

09 ;

摘要：

In the search for new chemical entities that can control resistant weeds by addressing novel modes of action (MoAs), we were interested in further exploring a compound class that contained a 1,8-naphthyridine core. By leveraging scaffold hopping methodologies, we were able to discover the new thiazolopyridine compound class that act as potent herbicidal molecules. Further biochemical investigations allowed us to identify that the thiazolopyridines inhibit acyl-acyl carrier protein (ACP) thioesterase (FAT), with this being further confirmed via an X-ray cocrystal structure. Greenhouse trials revealed that the thiazolopyridines display excellent control of grass weed species in pre-emergence application coupled with dose response windows that enable partial selectivity in certain crops.

引用

页码：18212 / 18226

页数：15

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