Pyridine and Thiazole‐Containing Insecticides as Potent Agonists on Insect Nicotinic Acetylcholine Receptors

2019

Chimia

Discovery background, lead optimization pathways, synthesis and structure–activity relationships of three different research projects searching for new active ingredients against downy mildew diseases are reported. These case studies, on which the author worked in three different decades in the research departments of Syngenta Crop Protection AG and its legacy company Novartis Crop Protection AG deal with inhibitors of cellulose synthase, tubulin polymerization and oxysterol-binding protein. Rarely used reactions, which have been applied within these projects, such as Seebach's variation of the Passerini reaction, the Bogert quinazoline synthesis and the carbonyldiimidazole-mediated Lossen rearrangement give proof of the significance of synthetic organic chemistry for modern crop protection.

Section: S: Inhibitors Of Oxysterol-binding Proteinmentioning

confidence: 99%

Episodes from the Continuous Search for Solutions against Downy Mildew Diseases

2019

Chimia

“…This is indeed the case, and therefore, the chlorothiazole ring of thiamethoxam ( 46 ) is an ideal mimic of the chloropyridyl moiety of neonicotinoid insecticide imidacloprid ( 45 ). Interestingly, both aromatic and saturated rings of imidacloprid have been replaced in thiamethoxam by an isosteric heterocycle with a different ring size: the six-membered ring by a five-membered ring and the five-membered ring by a six-membered ring. , In the same context, also, pyrimidine and thiadiazole are true bioisosteres as well. The pyrimidine derivative 47 and its thiadiazole analogue 48 are both discovery milestones in the invention pathway to nematicide fluensulfone (Scheme ).…”

Section: Replacement Of a Heterocycle By Another Heterocyclic Ringmentioning

confidence: 99%

Isosteric Ring Exchange as a Useful Scaffold Hopping Tool in Agrochemistry

2023

J. Agric. Food Chem.

Replacing one ring in a molecule by a different carba- or heterocycle is an important scaffold hopping manipulation, because biologically active compounds and their analogues, which underwent such a transformation, are often similar in size, shape, and physicochemical properties and, therefore, likely in their potency as well. This review will demonstrate, how isosteric ring exchange led to the discovery of highly active agrochemicals and which ring interchanges have proven to be most successful.

“…, in which an acyclic aminal replaces the imidazolidine of the lead compound 38. 46,47 These neonicotinoids are agonists of the insect nicotinic acetylcholine receptor and share this mode of action with the natural product nereistoxin (51), which is found in marine annelid worms of the species Lumbriconereis heteropoda. In the commercialized insecticide cartap (52), the 1,2-dithiolane ring of nereistoxin has been opened to a bisthiocarbamate.…”

Section: Ring Opening: Generation Of Pseudo-ring Structuresmentioning

confidence: 99%

“…The opposite of the above-described ring closure options of lead compounds is the ring opening of a carba- or heterocycle in a biologically active molecule, which often results in pseudo-ring structures. For example, the neonicotinoid insecticide nitenpyram ( 50 ) can be seen as a ring-opened analogue of NTN32692 ( 38 ), in which an acyclic aminal replaces the imidazolidine of the lead compound 38 . , These neonicotinoids are agonists of the insect nicotinic acetylcholine receptor and share this mode of action with the natural product nereistoxin ( 51 ), which is found in marine annelid worms of the species Lumbriconereis heteropoda. In the commercialized insecticide cartap ( 52 ), the 1,2-dithiolane ring of nereistoxin has been opened to a bis-thiocarbamate. , The discovery of the chitin-synthesis-inhibiting mite growth inhibitor hexythiazox ( 54 ) started with the thiazolotriazinedione derivative 53 , which by opening of the triazine ring delivered hexythiazox. , The experimental insecticide PH-6042 ( 55 ) was the starting point in the search for novel voltage-dependent sodium channel blockers with activity against Lepidoptera and Coleoptera species.…”

Section: Ring Opening: Generation Of Pseudo-ring Structuresmentioning

confidence: 99%

Ring Closure and Ring Opening as Useful Scaffold Hopping Tools in Agrochemistry

2023

J. Agric. Food Chem.

Ring closing acyclic parts of a molecular scaffold or the opposite manipulation, opening rings to produce pseudo-ring structures, is an important scaffold hopping manipulation. Analogues derived from biologically active compounds through the utilization of such strategies are often similar in shape and physicochemical properties and, therefore, likely to exhibit similar potency. This review will demonstrate how several different ring closure techniques, such as replacing carboxylic functions by cyclic peptide mimics, incorporating double bonds into aromatic rings, tying back ring substituents to a bicyclic structure, cyclizing adjacent ring substituents to an annulated ring, bridging annulated ring systems to tricyclic scaffolds, and exchanging gem-dimethyl groups by cycloalkyl rings, but also ring opening led to the discovery of highly active agrochemicals.