Mingzhen Mao

Synthesis and insecticidal evaluation of novel N-pyridylpyrazolecarboxamides containing cyano substituent in the ortho-position

In an attempt to search for potent insecticides targeting the ryanodine receptor (RyR), a series of novel N-pyridylpyrazolecarboxamides containing cyano substituent in the ortho-position were designed and synthesized. Their insecticidal activities of target compounds against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) indicated that most of the compounds showed moderate to high activities at the tested concentrations. In particular, compound 6l and 6o showed 86% larvicidal activities against Plutella xylostella at the concentration of 0.1mg/L, while the activity of compound 6h against Mythimna separate was 80% at 1mg/L. The calcium imaging technique was applied to investigate the effects of some title compounds on the intracellular calcium ion concentration ([Ca(2+)](i)), experimental results demonstrated that compound 6h stimulates a transient elevation in [Ca(2+)](i) in the absence of external calcium after the central neurons dye loading with fluo-3 AM. However, when the central neurons were dyed with fluo-5N and incubated with 2-APB, [Ca(2+)]i decreased transiently by treated of compound 6h. All of the calcium imaging technique experiments demonstrated that these novel compounds deliver calcium from endoplasmic reticulum to cytoplasm, which proved that the title compounds were the possible activators of insect RyR.

Modulations of high-voltage activated Ca2+ channels in the central neurones of Spodoptera exigua by chlorantraniliprole

The modulation of voltage‐gated calcium channels by chlorantraniliprole in the central neurones isolated from third‐instar larvae of Spodoptera exigua is studied by the whole‐cell patch‐clamp technique. The current of calcium in the third‐instar larvae of S. exigua is identified as a high‐voltage activated Ca2+ current. During the 10‐min recording, the current–voltage relationship curves of whole‐cell calcium channels are shifted in a negative direction by 10 mV compared with the control group. The fact that the gravity rundown of calcium current in the treated group is more apparent than in the control group demonstrates that the open channels are constantly inactivated. In addition, chlorantraniliprole inhibits the recorded calcium currents in a concentration‐dependent manner, which is irreversible on washout.

Synthesis and insecticidal evaluation of novel N-pyridylpyrazolecarboxamides containing an amino acid methyl ester and their analogues.

On the basis of the commercial insecticide chlorantraniliprole, a series of novel N-pyridylpyrazolecarboxamides containing an amino acid methyl ester and their analogues were designed and synthesized. Their chemical structures were established on the basis of corresponding (1) H NMR spectroscopy, (13)C NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction analysis. The insecticidal activities of the new compounds against oriental armyworm ( Mythimna separata ) and diamondback moth ( Plutella xylostella ) were evaluated. The results of bioassays indicated that most of the compounds showed moderate to high activities at the tested concentration, of which the compounds 6 containing a methyl acrylate substructure had excellent larvicidal activity; for example, 6a displayed 100% larvicidal activity against P. xylostella at the concentration of 0.005 mg/L, whereas the activities of both compounds 6g and 6h against M. separata were 100% at 2.5 mg/L. The calcium imaging technique experiment results showed that novel compound 6 could elevate the calcium concentration in the cytoplasm. Furthermore, this study also provided evidence that compound 6h activates inositol 1,4,5-trisphosphate (IP3) sensitive intracellular calcium release channels in the endoplasmic reticulum of Spodoptera exigua third-instar larva neurons.

Synthesis and insecticidal evaluation of novel anthranilic diamides containing N-substitued nitrophenylpyrazole.

To cope with developing pest resistance and ecological problems associated with conventional insecticides and to search for potent insecticides targeting at ryanodine receptor (RyR), a series of novel anthranilic diamides containing N-substitued nitrophenylpyrazole were designed and synthesized. The insecticidal activities of target compounds against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) were evaluated in our greenhouse by bio-assay tests and the relative structure-activity relationships were briefly discussed. Most compounds exhibited moderate to high activities, in which G₇ and K₅ showed high activity against oriental armyworm and K₂ and K₄ against diamondback moth even better than the control-chlorantraniliprole. The calcium imaging technique was used to investigate the effects of several typical title compounds on the [Ca(2+)](i), especially the effects of G₇ on the intracellular calcium ion concentration ([Ca(2+)](i)) in neurons, which indicated that some title compounds were potent activators of the RyR.

Synthesis and biological activity of novel 1-substituted phenyl-4-[N-[(2'-morpholinothoxy)phenyl]aminomethyl]-1H-1,2,3-triazoles.

In an attempt to search for potent antifungal agents, a series of novel 1‐substituted phenyl‐4‐[N‐[(2′‐morpholinothoxy)phenyl]aminomethyl]‐1H‐1,2,3‐triazoles 5a–m was designed and synthesized via Huisgen cycloaddition reaction between various (2‐morpholinoethoxy)‐N‐(prop‐2‐ynyl)aniline and different azidobenzene. Their chemical structures were characterized by 1H NMR and elemental analysis. A cleaner reaction with milder conditions and satisfactory yields was observed in the micorwave‐assisted synthesis of 4a–c. The fungicidal activity of some target compounds were evaluated in vitro against Fusarium omysporum, Physalospora piricola, Alternaria solani, Cercospora arachidicola and Gibberella zeae at 50 μg/mL. The bioassay results indicated that some compounds exhibited moderate fungicidal activities. Furthermore, compound 5h displayed equal activity to the positive control compounds against Alternaria solani.

Synthesis and biological activity of novel 1-substituted phenyl(glycosyl)-4-{4-[4,6-dimethoxy)pyrimidin-2-yl] piperazin-1-yl}methyl-1 H -1,2,3-triazoles

A series of novel 1-substituted phenyl or glycosyl 1,2,3-triazoles was designed and synthesized by azide-alkyne 1,3-dipolar cycloaddition between 4,6-dimethoxy-2-[4-prop-2-ynyl)piperazin-1-yl] pyrimidine and each of different azides catalysed by in situ generated Cu(I). The O-acyl protecting groups on glycosyl 1,2,3-triazoles were removed by triethylamine in wet methanol. Their chemical structures were established on the basis of corresponding 1H NMR, 13C NMR, MS and elemental analysis. The fungicidal activities of target compounds were evaluated in vitro against Fusarium omysporum, Physalospora piricola, Alternaria solani, Phytophthora capsici, Cercospora arachidicola and Gibberella zeae at 50 μg/mL. The bioassay results indicate that some of the compounds exhibited moderate but promising fungicidal activities. In particular, acetylated glucopyranosyl triazole displayed a good fungicidal activity against Physalospora piricola, which is equal to that of the positive control compound chlorothalonil.

Design, Synthesis and Structure-activity of N -Glycosyl-1-pyridyl-1 H -pyrazole-5-carboxamide as Inhibitors of Calcium Channels

Carbohydrates, with broad-spectrum structures and biological functions, are key organic compounds in nature, along with nucleic acids and proteins. As part of our ongoing efforts to develop a new class of pesticides with novel mechanism of action, a series of novel N-glycosyl-1-pyridyl-1H-pyrazole-5-carboxamide was designed and synthesized via the reactions of glycosyl methanamides and pyridyl-pyrazole acid. The compounds were characterized by 1H NMR and 13C NMR. The bioassay results indicate that some of these compounds exhibit moderate insecticidal activities and assessed as potential inhibitors of calcium channels. The modulation of voltage-gated calcium channels by compounds 4a and 5a in the central neurons isolated from the third instar larvae of Spodoptera exigua was studied by whole-cell patch-clamp technique. In addition, compound 5a inhibits the recorded calcium currents reversible on washout. Experimental results also indicate that compound 5a did not release stored calcium from the Endoplasmic Reticulum. The present work demonstrates that N-glycosyl-1-pyridyl-1H-pyrazole-5-carboxamides cannot be used as possible inhibitors of calcium channels for developing novel pesticides.

Regioselective Synthesis of Novel 3‐Thiazolidine Acetic Acid Derivatives from Glycosido Ureides

A series of 3‐thiazolidine acetic acid‐2‐(per‐O‐acetylglycosyl)‐1′‐imino‐α‐(substituted)‐4‐oxo ethyl ester derivatives (3a–t) were prepared via the reaction of substituted amino acid‐N‐[(per‐O‐acetylglycosylamino)thioxomethyl]‐ethyl ester with ethyl bromoacetate. The crystal structure of 3‐thiazolidine acetic acid‐2‐(2′,3′,4′,6′‐tetra‐O‐acetyl‐β‐d‐galactoyranosyl)‐1′‐imino‐α‐methyl‐4‐oxo ethyl ester 3g and 1H‐13C HMBC (2D NMR experiments) measurements of 3‐thiazolidine acetic acid‐2‐(2′,3′,4′,6′‐tetra‐O‐acetyl‐β‐d‐galactopyranosyl)‐1′‐imino‐α‐(1‐methylthio)ethyl‐4‐oxo ethyl ester 3j revealed the exclusive regioselectivity during the closure of these rings toward the N‐2 position of the thiourea moiety. Furthermore, the crystal structure of compound 3g showed that the attack of N‐1 was blocked by sugar ring owing to the steric effect. The bioactivity data suggested that compound 2e has mild anticancer activity.

Synthesis and biological evaluation of novel N-pyridylpyrazolecarboxamides containing benzothiazole

GRAPHICAL ABSTRACT ABSTRACT A series of novel N-pyridylpyrazolecarboxamides containing benzothiazole were designed and synthesized. The target compounds were identified by 1H NMR,13C-NMR, IR, high-resolution mass spectrum (HRMS) and elemental analysis. The bioactivities of the new compounds against oriental army worm (Mythimnaseparata) and diamond back moth (Plutellaxylostella) were evaluated. The results of bioassays indicated that some of the compounds showed good activitiesat the tested concentrations. Compound Ij showed 100% larvicidal activities against Plutellaxylostella at 2.5 mg/L, while the activity of Ij against Mythimnaseparata was 100% at 10 mg/L.

Synthesis and pesticidal activities of novel anthranilic diamides containing pyridylpyrazole and iminodithiocarbamate or thiosemicarbazone motifs

Abstract A series of novel anthranilic diamide derivatives containing pyridylpyrazole and iminodithiocarbamate or thiosemicarbazone motifs were synthesized via multi-step reactions. The structures of seven title compounds (methyl 2-(2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamido)-5-chloro-3- methylbenzylidene)hydrazinecarbodithioate 7 and 3-bromo-N-(2-((2-substitutedcarbamothioylhydrazono)methyl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide 8a-8f) were confirmed by melting points, IR, 1H NMR, 13C NMR, and HRMS. The bioassays showed that some of the compounds exhibited modest insecticidal activities against oriental armyworm (Mythimna separata Walker), particularly, compound 8b (3-bromo-N-(4-chloro-2-methyl-6-((2-(methylcarbamothioyl)hydrazono)methyl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide) held 100% and 30% larvicidal activity at the concentration of 25 mg/L and 10 mg/L, respectively. In addition, several compounds displayed favorable fungicidal activities against Alternaria solani Sorauer and Physalospora piricola at 50 μg/mL, and were comparable with the controls Chlorothalonil and Triadimefon. The results in this paper will provide important information for further research and development of sulfur-containing heterocyclic agrochemicals. Graphical Abstract