Reversal of Functional Groups as a Useful Scaffold Hopping Tool in Agrochemistry

Abstract

Reverting the orientation of a functional group by exchanging molecular parts of it is an important scaffold hopping manipulation, as biologically active compounds and their analogs, which underwent such a transformation, are often similar in shape and physicochemical properties and therefore likely in their potency as well. This review will demonstrate, how the inversion of carboxamides, sulfonamides, carbamates, oximes, hydrazones, O,S-acetals, and ethers led to the discovery of highly active agrochemicals.

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

“…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. The crucial scaffold hopping approach, which led from PH-6042 ( 55 ) to metaflumizone ( 56 ), was the ring opening of the pyrazoline scaffold. , Finally, the phenylendiamine bis-thiourea derivative thiophanate-methyl ( 58 ) can be seen as a ring-opened variation of the benzimidazole fungicide benomyl ( 57 ) (Scheme ). , …”

“…The crucial scaffold hopping approach, which led from PH-6042 (55) to metaflumizone (56), was the ring opening of the pyrazoline scaffold. 52,53 Finally, the phenylendiamine bis-thiourea derivative thiophanate-methyl (58) can be seen as a ring-opened variation of the benzimidazole fungicide benomyl (57) (Scheme 10). 37, 54 A further successful ring-opening approach has been described in the field of oxysterol-binding protein inhibitors.…”

Design, Synthesis, and Antifungal Activities of Novel Pyrazole-4-carboxamide Derivatives Containing an Ether Group as Potential Succinate Dehydrogenase Inhibitors

“…Incorporation of two or more pharmacophores of bioactive scaffolds based on molecular hybridization has been one of the most successful strategies for the discovery of new pesticides and drugs. − For example, flubeneteram, a novel commercial SDHI fungicide approved recently (Figure ), was discovered through pharmacophore-linked fragment virtual screening (PFVS) by the Yang group, − which could be considered as a combination of pyrazole-4-carboxamide and diphenyl ether bioactive scaffolds based on the molecular hybridization strategy. Scaffold hopping, another widely exploited design approach, offers the opportunity to modify known lead compounds to afford novel structures with high potency, low toxicity, and enhanced physicochemical properties. − In this work, in search of novel SDHIs, flubeneteram was used as lead compounds, and we attempted to replace the diphenyl ether scaffold of flubeneteram with extended phenyl diether and aliphatic ether by scaffold hopping (Figure ). A series of novel pyrazole-4-carboxamide derivatives bearing an extended ether group were designed and synthesized by a simple synthetic method (Figure ).…”

Isosteric Ring Exchange as a Useful Scaffold Hopping Tool in Agrochemistry

“…The isosteric ring exchange, which has been successfully used in medicinal chemistry − as well as in crop protection chemistry, has never been reviewed thus far for agrochemistry; therefore, this review summarizes important applications of it in crop protection. Other specific scaffold hopping techniques, which have been recently summarized regarding their use in agrochemistry, are the reversal of functional groups and the insertion of small flexible linkers …”