25288-48-6

Usage

Purpose

Herbicide to control weeds in various crops

Chemical class

Acetanilides, chloroacetanilide herbicide

Mode of action

Inhibits cell division and growth in susceptible plants, leading to their death

Application

Applied to the soil and absorbed by the roots of germinating seeds

Effects on plants

Interferes with lipid synthesis and disrupts cell membranes

Primary crops

Soybeans, peanuts, and cotton

Effective against

Problematic weeds such as pigweed and nightshade

Safety concerns

Potential toxicity and environmental impact, must be handled and used with caution and in accordance with safety guidelines.

Upstream product

• 462-08-8 pyridin-3-ylamine 
• 588-32-9 3-chlorophenoxyacetic acid 

Relevant academic research and scientific papers

Discovery of 2-phenoxyacetamides as inhibitors of the Wnt-depalmitoleating enzyme NOTUM from an X-ray fragment screen

NOTUM is a carboxylesterase that has been shown to act by mediating the O-depalmitoleoylation of Wnt proteins resulting in suppression of Wnt signaling. Here, we describe the development of NOTUM inhibitors that restore Wnt signaling for use in in vitro disease models where NOTUM over activity is an underlying cause. A crystallographic fragment screen with NOTUM identified 2-phenoxyacetamide 3 as binding in the palmitoleate pocket with modest inhibition activity (IC50 33 μM). Optimization of hit 3 by SAR studies guided by SBDD identified indazole 38 (IC50 0.032 μM) and isoquinoline 45 (IC50 0.085 μM) as potent inhibitors of NOTUM. The binding of 45 to NOTUM was rationalized through an X-ray co-crystal structure determination which showed a flipped binding orientation compared to 3. However, it was not possible to combine NOTUM inhibition activity with metabolic stability as the majority of the compounds tested were rapidly metabolized in an NADPH-independent manner.