ABSTRACT
In order to discover new antifungal agrochemicals that could have highly active and novel motifs, thirty-six new 2-acylaminocycloalkylsulfonamides (IV) were synthesized. Their structures were characterized and confirmed by 1H NMR, 13C NMR, IR, MS, elemental analysis and X-ray single crystal diffraction. In vitro and in vivo activities against various Botrytis cinerea strains were evaluated. Bioassay results revealed that most of the title compounds exhibited excellent in vitro fungicidal activity, in which compound IV-26 showed the highest activity against sensitive, low-resistant, moderate-resistant and high-resistant strains of B. cinerea compared with the positive fungicide procymidone. Meanwhile in vivo fungicidal activity of compound IV-31 was better than the commercial fungicides procymidone and chesulfamide in greenhouse trial. The structure activity relationship (SAR) was also discussed and the results were of importance to the structural optimization and development of more potent sulfonamides antifungal agents.
Subject(s)
Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Botrytis/drug effects , Fungicides, Industrial/chemistry , Sulfonamides/chemistry , Sulfonamides/pharmacology , Antifungal Agents/chemical synthesis , Chemistry Techniques, Analytical , Cucumis/microbiology , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/pharmacology , Microbial Sensitivity Tests , Microbial Viability/drug effects , Plant Diseases/prevention & control , Seedlings/microbiology , Structure-Activity RelationshipABSTRACT
A series of novel 2-substituted aminocycloalkylsulfonamides were designed and synthesized by highly selective N-alkylation reaction, whose structures were characterized by 1H NMR, 13C NMR and HRMS. Among them, the configuration of compounds III12 and III20 were confirmed by X-ray single crystal diffraction. Bioassays demonstrated that the title compounds had considerable effects on different strains of Botrytis cinerea and Pyricularia grisea. Comparing with positive control procymidone (EC50=10.31mg/L), compounds III28, III29, III30 and III31 showed excellent fungicidal activity against a strain of B. cinerea (CY-09), with EC50 values of 3.17, 3.04, 2.54 and 1.99mg/L respectively. Their in vivo fungicidal activities were also better than the positive controls cyprodinil, procymidone, boscalid and carbendazim in pot experiments. Moreover, the fungicidal activity of III28 (EC50=4.62mg/L) against P. grisea was also better than that of the positive control isoprothiolane (EC50=6.11mg/L). Compound III28 would be great promise as a hit compound for further study based on the structure-activity relationship.
Subject(s)
Botrytis/drug effects , Drug Design , Fungicides, Industrial/pharmacology , Pyricularia grisea/drug effects , Sulfonamides/pharmacology , Thiazoles/pharmacology , Dose-Response Relationship, Drug , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/chemistry , Thiazoles/chemical synthesis , Thiazoles/chemistryABSTRACT
We report a true MCR involving the reaction of N-(prop-2-ynyl)quinoxalin-2-amine derivatives with 2-iodoanilines and tosyl azide in the presence of 10 mol% of CuI and Et3N in DMSO to afford the pre-designed hybrid molecules containing quinoxaline framework linked with a benzimidazole nucleus. The MCR proceeds in the absence of any ligand and/or lateral addition of the catalyst/base affording products within 30 min in good yields, some of which showed encouraging apoptosis inducing properties in zebrafish.
Subject(s)
Apoptosis , Benzimidazoles/chemistry , Quinoxalines/chemistry , Animals , Catalysis , Copper/chemistry , Dose-Response Relationship, Drug , Drug Design , Ethylamines/chemistry , Humans , Iodides/chemistry , Ligands , Microscopy, Fluorescence , Neoplasms/drug therapy , Neoplasms/metabolism , ZebrafishABSTRACT
For the first time TFAA/H3PO4 has facilitated the direct and metal-free N-acylation of carbazoles leading to a number of N-acylated derivatives. Several of these compounds were found to be promising when tested for their anti-proliferative properties against oral cancer cell lines.
Subject(s)
Acetic Anhydrides/chemistry , Carbazoles/pharmacology , Fluoroacetates/chemistry , Neoplasms/pathology , Phosphoric Acids/chemistry , Small Molecule Libraries/pharmacology , Acylation , Carboxylic Acids/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , HEK293 Cells , Humans , Small Molecule Libraries/chemistry , StereoisomerismABSTRACT
A series of 1,3-disubstituted pyrrolo[2,3-b]quinoxalines has been designed for the potential inhibition of PDE4 without inhibiting luciferase. A ligand/PTC (phase transfer catalyst) free intramolecular Heck cyclization strategy was used to prepare these compounds, some of which showed significant inhibition of PDE4B (IC50≈ 5-14 µM) and growth inhibition of oral cancer cells (CAL 27) but not inhibition of luciferase in vitro. They also showed acceptable safety profiles but no apoptosis in zebrafish embryos.
