A series of novel title compounds 6a-6r and 7a-7c have been synthesized by Mannich reaction of the new triazole Schiff base intermidiates, substituted piperazine and formaldehyde under mild conditions in excellent yie...A series of novel title compounds 6a-6r and 7a-7c have been synthesized by Mannich reaction of the new triazole Schiff base intermidiates, substituted piperazine and formaldehyde under mild conditions in excellent yields. The crystal structure of compound 6i was determined to show a chair conformation of the piperazine ring and an （E）-configuration of the C=N double bond. The bioassay results indicated that most of the newly synthesized compounds exhibited excellent in vitro inhibitory activities and broader spectrum against several plant fungi, and were more effective than the control Triadimefon. Several compounds also displayed favourable in vivo antifungal activities. The relationships between the compound structures and various biological activities were discussed. Furthermore, the CoMFA calculation based on the antifungal activity data of compounds 6 against R. cerealis was carried out to establish a 3D-QSAR model, which revealed that steric and electrostatic fields were two most important factors for contributing the bioactivity of the compounds. The present work will provide significant information for guiding optimization of such new structures to develop novel agrochemicals with higher antifungal activities.展开更多
In order to discover new generation of triazole antifungal agents,a series of novel antifungal triazoles were designed and synthesized by structural simplification of our previously identified triazolepiperdine-hetero...In order to discover new generation of triazole antifungal agents,a series of novel antifungal triazoles were designed and synthesized by structural simplification of our previously identified triazolepiperdine-heterocycle lead compounds.Several target compounds showed good antifungal activity with a broad spectrum.In particular,compound 71 was highly active against Candida albicans and Candida glabrata.Moreover,compound 71 showed potent in vivo antifungal efficacy in the Caenorhabditis elegans-C.albicans infection model.展开更多
A series of novel triazole derivatives containing y-lactam were designed and synthesized, and their structures were confirmed by IH NMR, 13C NMR and HRMS, The in vitro antifungal activities of the target compounds wer...A series of novel triazole derivatives containing y-lactam were designed and synthesized, and their structures were confirmed by IH NMR, 13C NMR and HRMS, The in vitro antifungal activities of the target compounds were evaluated, The results showed that all of the compounds exhibited stronger activity against the six clinically important fungi tested than fluconazole. 3D and 3E showed comparative activity against the fungi tested except for Candida glabrata and Aspergillus fumigatus as voriconazole. In addition, the docking model for 2A and CYP51 was investigated.展开更多
基金supported by the National Natural Science Foundation of China(No. 21372133)Tianjin Natural Science Foundation(No. 17JCYBJC19900)
文摘A series of novel title compounds 6a-6r and 7a-7c have been synthesized by Mannich reaction of the new triazole Schiff base intermidiates, substituted piperazine and formaldehyde under mild conditions in excellent yields. The crystal structure of compound 6i was determined to show a chair conformation of the piperazine ring and an （E）-configuration of the C=N double bond. The bioassay results indicated that most of the newly synthesized compounds exhibited excellent in vitro inhibitory activities and broader spectrum against several plant fungi, and were more effective than the control Triadimefon. Several compounds also displayed favourable in vivo antifungal activities. The relationships between the compound structures and various biological activities were discussed. Furthermore, the CoMFA calculation based on the antifungal activity data of compounds 6 against R. cerealis was carried out to establish a 3D-QSAR model, which revealed that steric and electrostatic fields were two most important factors for contributing the bioactivity of the compounds. The present work will provide significant information for guiding optimization of such new structures to develop novel agrochemicals with higher antifungal activities.
基金supported by the National Natural Science Foundation of China(Nos.81573283,21502224)the 863 Hi-Tech Program of China(No.2014AA020525)the Shanghai"ShuGuang"Project(No.14SG33)
文摘In order to discover new generation of triazole antifungal agents,a series of novel antifungal triazoles were designed and synthesized by structural simplification of our previously identified triazolepiperdine-heterocycle lead compounds.Several target compounds showed good antifungal activity with a broad spectrum.In particular,compound 71 was highly active against Candida albicans and Candida glabrata.Moreover,compound 71 showed potent in vivo antifungal efficacy in the Caenorhabditis elegans-C.albicans infection model.
基金supported by the National Natural Science Foundation of China (No. 21402223)
文摘A series of novel triazole derivatives containing y-lactam were designed and synthesized, and their structures were confirmed by IH NMR, 13C NMR and HRMS, The in vitro antifungal activities of the target compounds were evaluated, The results showed that all of the compounds exhibited stronger activity against the six clinically important fungi tested than fluconazole. 3D and 3E showed comparative activity against the fungi tested except for Candida glabrata and Aspergillus fumigatus as voriconazole. In addition, the docking model for 2A and CYP51 was investigated.
