ChemInform Abstract: Insecticidal Pyrroles: Discovery and Overview

Addor, R. W.; Babcock, T. J.; Black, Bruce C.; Brown, Dean G.; Diehl, R. E.; Furch, Joseph A.; Kameswaran, V.; Kamhi, V. M.; Kremer, Kenneth A. M.; Kuhn, D. G.; Lovell, J. B.; Lowen, Gregory T.; Miller, T. P.; Peevey, R. M.; Siddens, J. K.; Treacy, M. F.; Trotto, S. H.; Wright, Damian P.

doi:10.1002/chin.199343330

Cited by 6 publications

(7 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dioxapyrrolomycin (Figure ) is an antibiotic and insecticidal pyrrole NP isolated from the fermentation of Streptomyces f umanus . , Whereas possessing moderate insecticidal activity, it also exhibited high mouse oral toxicity, rendering it unsuitable as a crop protection product. , However, dioxapyrrolomycin did serve as the inspiration for the discovery and development of the insecticidal pyrroles. The pyrrole portion of the NP was chosen as the starting point for a synthesis effort that saw the substitution pattern on the pyrrole optimized by incorporating a phenyl moiety.…”

Section: Insecticidesmentioning

confidence: 99%

“…The pyrrole portion of the NP was chosen as the starting point for a synthesis effort that saw the substitution pattern on the pyrrole optimized by incorporating a phenyl moiety. These synthetic explorations ultimately gave rise a pyrrole-based pro-insecticide, chlorfenapyr (Figure ) − that was structurally simpler, more efficacious, and exhibited a more favorable toxicological profile than dioxapyrrolomycin.…”

Section: Insecticidesmentioning

confidence: 99%

See 1 more Smart Citation

Structure Simplification of Natural Products as a Lead Generation Approach in Agrochemical Discovery

Sparks¹,

Duke

2021

J. Agric. Food Chem.

103

View full text Add to dashboard Cite

Natural products (NPs) have a long history as sources of compounds for crop protection. Perhaps a more important role for NPs has been as models and inspiration for the discovery and development of synthetic crop protection compounds. NPs and their synthetic mimics account for 18% of all crop protection compounds, whereas another 38% of all crop protection compounds have a NP that could have served as a model. Because NPs are often complex molecules, have limited availability, or possess structural features that constrain their suitability for use in agricultural settings, a key element in NP-inspired compounds is the simplification of the NP structure to provide a synthetically accessible molecule that possesses the physicochemical properties needed for use in crop protection. Herein we review a series of examples of NP mimics that demonstrate the structural or synthetic simplification of NPs as a guide for the discovery of future NP-inspired agrochemicals focused on fungicides, herbicides, and insecticides.

show abstract

Section: Insecticidesmentioning

confidence: 99%

Section: Insecticidesmentioning

confidence: 99%

Structure Simplification of Natural Products as a Lead Generation Approach in Agrochemical Discovery

Sparks¹,

Duke

2021

J. Agric. Food Chem.

103

View full text Add to dashboard Cite

show abstract

“…Although dioxapyrrolomycin ( 90 ), isolated from the fermentation broth of Streptomyces fumanus , had broad but moderate insecticidal and acaricidal activity as an uncoupler of oxidative phosphorylation, its relatively high oral mammalian toxicity precluded it from being developed. A synthesis program with the aim to optimize the insecticidal activity while reducing the mammalian toxicity resulted in chlorfenapyr ( 91 ) . The observation that feeding on diseased marine annelid worms of the species Lumbriconeris heteropoda is lethal to flies led to the subsequent isolation and identification of nereistoxin ( 92 ), which acts at the neuronal nicotinic acetylcholine receptor (nAChR).…”

Section: Scaffold Hopping From Naturementioning

confidence: 99%

Agrochemical lead optimization by scaffold hopping

Lamberth

2017

Pest Management Science

View full text Add to dashboard Cite

Scaffold hopping, the exchange of a specific portion of a potential active ingredient with another substructure with the aim of finding isofunctional molecular structures with significantly different molecular backbones, often offers the chance in lead discovery or optimization to mitigate problems related to toxicity, intellectual property, and insufficient potency or stability. Scaffold hopping tools such as isosteric ring replacement including 1,3 nitrogen shift and cyclic imine-amide isosterism, but also ring opening and ring closure approaches, functional group isosterism, reversion of functional groups, chain shortening, chain lengthening, and scaffolds delivered by natural products, have become a permanent fixture of the innovation and optimization process in crop protection research. Their appropriate use will be explained through examples of success stories in the field of agrochemistry. Analogies to, but also differences from, the main categories of scaffold hopping in medicinal drug discovery are discussed. © 2017 Society of Chemical Industry.

show abstract

“…Further testing confirmed that chlorfenapyr was indeed a proinsecticide, with the parent compound showing essentially no uncoupling activity before activation. 40,41 Oxidases have been implicated as necessary for this activation by an observed reduction in toxicity in insects pretreated with PBO. The oxidases required to activate chlorfenapyr can also be involved in resistance through the deactivation of other insecticides.…”

Section: Group 13: Uncouplers Of Oxidative Phosphorylation Via Disrupmentioning

confidence: 99%

Chance and design in proinsecticide discovery

Salgado

David

2017

Pest Management Science

View full text Add to dashboard Cite

Many insecticides are inactive on their target sites in the form that is sold and applied, needing first to be bioactivated. This proinsecticide strategy has often been achieved by design, through systematic derivatization of intrinsically active molecules with protecting groups that mask their toxic effects until their selective removal in target insects by metabolic enzymes generates the toxiphore. Proinsecticides can be designed to gain selectivity between target and non-target organisms, or to improve bioavailability by enhancing plant or insect uptake. In most cases, however, chance trumps design in proinsecticide discovery: most first-in-class products that we now know to be proinsecticides were only discovered a posteriori to be such, often after having been on the market for years. Knowing the active form of an insecticide is essential to mode of action identification, and early mode of action studies on novel chemotypes should take into account the possibility that the compounds might be proinsecticides. This paper reviews examples of proinsecticides in the marketplace, strategies for making proinsecticides and techniques for unmasking proinsecticides in mode of action studies. Our analysis of global agrochemical sales data shows that 34% of the dollar value of crop insecticides used in 2015 were proinsecticides. © 2016 Society of Chemical Industry.

show abstract

ChemInform Abstract: Insecticidal Pyrroles: Discovery and Overview

Cited by 6 publications

References 1 publication

Structure Simplification of Natural Products as a Lead Generation Approach in Agrochemical Discovery

Structure Simplification of Natural Products as a Lead Generation Approach in Agrochemical Discovery

Agrochemical lead optimization by scaffold hopping

Chance and design in proinsecticide discovery

Contact Info

Product

Resources

About