Design, Synthesis, Safener Activity, and Molecular Docking of Novel N‐Substituted Thiazide/Thiazole Derivatives

Abstract

A series of novel substituted thiazide/thiazole compounds were designed by splicing active groups and bioisosterism. The title compounds were synthesized via the cyclization, acylation, and carbamylation. All the compounds were characterized by IR, 1H‐NMR, 13C‐NMR, and HRMS. The single crystal of compound 3f was determined by X‐ray crystallography. The biological activity tests indicated that all the compounds showed potential safener activity to the herbicide chlorsulfuron, in which compound 3e showed almost the same level as the commercialized safener AD‐67. The molecular docking results were in good agreement with the bioassay results, which demonstrated that compound 3e might compete with chlorsulfuron in the acetolactate synthase active site, causing the herbicide ineffective in maize.

Herbicide Safeners: From Molecular Structure Design to Safener Activity

“…The MW, log p , HBAs, HBDs, RBs, and other physicochemical properties of compound 21 are close to those of chlorsulfuron, which has high detoxification potency. , The p K a , MW, and electronegativity of compound 8 were also similar to those of the herbicide, indicating great molecular-level similarity of the safener/herbicide . Additionally, both compound 8 and compound 21 were well aligned in a common skeleton with chlorsulfuron through comparison of molecular conformations. , Although the triazine and benzene rings did not exactly coincide, both aromatic rings provided a similar substitution (Figure c). , The same phenomenon was observed between compound 17 , cyprosulfamide (CSA), and diketonitrile (DKN). Compound 17 had better biological activity than CSA, probably because the former had a notably lower p K a than the latter, thereby favoring plant absorption and translocation .…”

“…The structure of chlorsulfuron contains phenyl, which rotates right at the active site, resulting in effectively blocking the channel entrance to prevent the substrate from binding to the active site and exerting herbicidal activity. Compound 21 partially blocks the channel entrance, due to the shift to the left of the phenyl portion at the active site (Figure c–e) . In contrast, the entire molecules of IDF and compound 19 rotated to the left at the active center, which only partially blocked the entrance (Figure f–h) …”

“…Various novel herbicide safeners have been designed and synthesized to solve chlorsulfuron injury to maize. Molecular docking models of compounds 6 , 7 , 19 , and 21 , IDF, and R-29148 with maize-derived ALS were constructed to speculate on the mechanism of action of different safeners. ,,,, Compound 6 interacted mainly with three amino acid residues in the ALS active site. As hydrogen-bond donors, Arg 377 and Ser 653 form hydrogen bonds with the oxygen atoms of compound 6 , while the isoxazole fraction formed π–π interactions with Trp 574, which exerted a significant effect on the ALS activity.…”

Research Progress in the Design and Synthesis of Herbicide Safeners: A Review

“…Ye and Fu’s team designed a series of sulfonylurea-substituted thiazide/thiazole compounds based on bioisosteric replacement, structure–activity relationships (SARs), and active subunit combination. , The sulfonylurea functional group was modified, and the sulfur- and nitrogen-containing heterocycle was retained (Scheme ). The results of the biological activity assay showed that the compound exhibited safener activity against chlorosulfuron.…”

Two-Dimensional Lead Halide Perovskites with Spirocyclic Intercalating Cations

“…The recently developed condensation method on thiol-containing organoammonium cations is a general and straightforward strategy for the construction of functional A-site cations for new TMHPs. , The reaction is driven by the condensation reaction between thiols on mercaptoethylamine (MEA) or mercaptoethylammonium halide salts (MEAX, X = halogen) and ketones and aldehydes, yielding predesigned dithioketal-containing intercalating cations. It is important to note that the zwitterionic form of MEA is also capable of reacting with ketones under mild conditions to form thiazolidine-derived structures. − Inspired by the ring-formation protocol, here, we further investigate the possibility of constructing new SC A-site cations using the thiazolidine-formation reactions between MEA and cyclic ketones (Figure ). Five types of SC cations were successfully made and used to construct corresponding TMHPs with well-defined structures with Ruddlesden–Popper (RP) and Dion–Jacobson (DJ) phases.…”