Microtubulin Assembly Inhibitors (Pyridines)

Heterocyclic chemistry in crop protection

“…) . Another example in which a carboxylic function of an active ingredient is successfully replaced by a heterocycle is the thioester–thiazoline exchange from dithiopyr ( 21 ) to thiazopyr ( 22 ), which both belong to the microtubulin‐assembly‐inhibiting herbicides …”

“…The pyridine building block 68 of the herbicide dithiopyr ( 21 ) is formed in only two steps from its tetrahydropyridine counterpart 67 . This saturated heterocycle, which can be obtained via Hantzsch cyclization in just one step from ethyl trifluoroacetoacetate, isovaleraldehyde and ammonia, is converted into the aromatic analog 68 in two steps via the corresponding dihydropyridine intermediate (Scheme ) . The concise synthetic approach to the insect repellent icaridin ( 71 ), which protects against bloodsucking arthropods, is based on the hydrogenation of 2‐pyridineethanol ( 69 ) to the corresponding piperidine derivative 70 …”

“…23 Another example in which a carboxylic function of an active ingredient is successfully replaced by a heterocycle is the thioester-thiazoline exchange from dithiopyr (21) to thiazopyr (22), which both belong to the microtubulin-assembly-inhibiting herbicides. 24 Heterocycles have a proven track record as ideal bioisosteric replacements of a benzene ring, partially because of the improvement in the physicochemical properties (see above), as a heterocycle in most cases is more polar than a similar substituted carbacyclic ring. There are several striking examples of how the biological activity of a lead compound could be dramatically enhanced by replacement of a benzene ring by a heterocycle.…”

Plant Health Management: Herbicides

“…The major symptom of affected plants is root clubbing as a result of isodiametric cell expansion from a lack of cortical microtublues (Lickfeldt et al, 2012). These dynamic structures form an intracellular network as part of the cytoskeleton that gives both stability and communication pathways within the cell.…”

“…The dinitroaniline herbicides bind specifically to the alpha subunit of the tubulin dimer in higher plants, preventing proper polymerization as demonstrated by in vitro experiments (Morejohn et al, 1987) and by analysis of weed-resistance mechanisms (Anthony et al, 1999;Hashim et al, 2012). The pyridine and benzamide herbicides do not bind to microtubules assemblies but rather are proposed to inhibit an unknown microtubule-associated protein (Lickfeldt et al, 2012). The pyridine and benzamide herbicides do not bind to microtubules assemblies but rather are proposed to inhibit an unknown microtubule-associated protein (Lickfeldt et al, 2012).…”