Synthesis and Insecticidal Evaluation of Novel Anthranilic Diamides Derivatives Containing 4‐Chlorine Substituted N‐Pyridylpyrazole

To search for potent insecticides targeting at ryanodine receptors (RyRs), a series of novel anthranilic diamides analogs containing 4‐chlorine N‐pyridylpyrazole were designed and synthesized. Their insecticidal activities were evaluated and the preliminary structure‐activity relationships (SARs) were discussed. The insecticidal results showed that some of the compounds (8a—8h, 8m, 8n) exhibited good larvicidal activities against oriental armyworm at 2.5 mg·L^–1, and compound 8m possessed 60% insecticidal activity at 0.5 mg·L^–1. For diamondback moth, 8m exhibited better activity than Chlorantraniliprole at a hundred fold preference. The calcium imaging technique experiment results suggested that compound 8m could increase the intracellular [Ca²⁺]_i. With the neurons preincubated experiment, the results confirmed that the target of this series of compounds could be RyRs in the central larvae neurons of oriental armyworm. The results indicated that compound 8m could respond as a potential modulator of the insect ryanodine receptor.     

Synthesis and Anti Tuberculostatic Activity of Novel 1,3,4‐Oxadiazole Derivatives

A series of novel 2,5‐disubstituted 1,3,4‐oxadiazole derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed interesting activity against a strain of Mycobacterium tuberculosis H₃₇Rv. The result of the antimycobacterial activity tests revealed that 2‐(2‐naphthyloxymethyl)‐5‐phenoxymethyl‐1,3,4‐oxadiazole ( IVd ) exhibited > 90% inhibition at MIC ?6.25.     

Synthesis and Bioactivity of Novel N,N′‐Diacylhydrazine Derivatives Containing Furan(I)

The furan ring system possesses electron‐rich properties and exhibits various biological activities, which was introduced into diacylhydrazine to create novel leading compounds that may serve as improved pesticides and pharmaceuticals. A series of novel diacylhydrazine derivatives containing a furan ring were synthesized by the reaction of 5‐fluorophenyl‐2‐furoyl chloride with substituted benzoylhydrazide in anhydrous dichloromethane under reflux. The structures of the resultant compounds were confirmed by IR, ¹H NMR, MS and elemental analysis. Insecticidal and anti‐tumor activities of these new compounds were evaluated.     

Synthesis and Antibacterial Activities of Novel Biphenyltetrazole Derivatives Bearing 1,3,4‐Oxadiazole

Several new 5‐[4′‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐ylsulfanylmethyl)‐biphenyl‐2‐yl]‐tetrazoles derivatives have been synthesized. The structures of these new compounds were confirmed by elementary analyses and spectral data. The antibacterial activities of the compounds were also evaluated.     

Synthesis and Bioactivity of Novel N,N′‐Diacylhydrazine Derivatives Containing Furan (III)

42 novel diacylhydrazine derivatives containing furan were synthesized by the reaction of 5‐substituted phenyl‐2‐furoyl chloride with substituted benzohydrazide in anhydrous dichloromethane under reflux. Their structures were confirmed by IR, ¹H NMR, MS and elemental analysis. Insecticidal and antitumor activity of these new compounds was evaluated. The preliminary bioassays showed that the target compounds exhibited larvicidal activity to the Mythimna separate, some of them exhibited good or moderate larvicidal activity. At the concentration of 0.1%, compounds I2 , I4 , I5 , and III1 showed 95.0%, 90.0%, 95.0% and 95.0% larvicidal activity to Mythimna separate respectively. Some compounds such as I2 , I4 , I5 and III1 showed the typical IGRs' activity, which could induce the larvae premature, abnormal, and lethal larval molt. Results of anticancer activity indicated that some compounds exhibited potential activity against some human cancer cell lines, for example, I1 and IV showed good activity to the BGC‐823 and the inhibitory rates were 60.86% and 61.94% respectively at 10 µmol/L.     

Synthesis and Characterization of Novel Stilbene Derivatives with 1,3,4‐Oxadiazole Unit

Four novel stilbene derivatives containing 1,3,4‐oxadiazole unit have been synthesized in four steps with overall yields (27～35%). The synthetic route involved one‐step installation of 2,5‐di‐p‐tolyl‐1,3,4‐oxadiazol via the direct coupling of p‐toluic acid with hydrazine hydrate promoted by PPA , benzylic bromination, conventional phosphonate formation, and Wittig‐Horner olefination.     

Design,Synthesis and Insecticidal Activity of Novel Anthranilic Diamides Containing Oxime Ester and Diacylhydrazine Moieties

Two series of novel anthranilic diamides containing oxime ester and diacylhydrazine moieties were designed and synthesized.Their structures were characterized by melting points,1H NMR,13C NMR and high resolution mass spectrometry（HRMS）.The single crystal structure of compound 7e was determined by X-ray diffraction and their evaluated insecticidal activity against oriental armyworm（Mythimna separata） indicates that some of the compounds exhibited moderate insecticidal activities.Among the 20 compounds,6a and 6b show 100％ larvicidal activity against Mythimna separate Walker at the test concentration of 100 mg/L.     

Synthesis and Cytotoxic Evaluation of Pyrrole Hetarylazoles Containing Benzimidazole/Pyrazolone/1,3,4‐Oxadiazole Motifs

Azomethine‐linked pyrrole bishetarylazoles containing benzimidazole/pyrazolone/1,3,4‐oxadiazole were synthesized in satisfactory yields. Their structures were confirmed by IR, ¹H‐NMR, ¹³C‐NMR, and elemental analysis. Evaluation for the cytotoxic activities in vitro against a panel of breast cancer cell lines (MDA‐AB‐231, BT‐474, and Ishikawa cells) revealed that the pyrrole–benzimidazole hybrids are more potent than the pyrazolone and 1,3,4‐oxadiazole hybrids in all cell lines. Compound 9 displayed promising cytotoxicity against BT‐474 cell line with IC₅₀ values, 7.7 µM.     

Synthesis,Nematicidal Activity,and 3D‐QSAR of Novel 1,3,4‐Oxadiazole/ Thiadiazole Thioether Derivatives

Forty one novel 1,3,4‐oxadiazole/thiadiazole thioether derivatives containing phenoxy moiety were designed and synthesized. Bioassay demonstrated that some of them showed remarkable activities against Tylenchulus semipenetrans in vitro and in vivo. Compounds 20 , 21 , 35 and 39 showed excellent lethal activities after treatment for 48 h in vitro, with LC₅₀ values of 13.4 ± 1.8, 11.7 ± 2.5, 13.7 ± 2.4 and 13.3 ± 1.1 mg·L^–1, respectively, which were obviously superior to fosthiazate (49.1 ± 2.8 mg·L^–1) and avermectin (26.6 ± 2.3 mg·L^–1). Compound 21 can effectively control the citrus nematode disease caused by T. semipenetrans at 200 mg·L^–1 in vivo with (68 ± 3)% inhibitory effect, which was even better than that of avermectin ((63 ± 2)%). The CoMFA and CoMSIA models of three‐dimensional quantitative structure‐activity relationships (3D‐QSARs) were established. The compound 33 was designed based on the 3D‐QSAR models with more vigorous nematicidal activities in vitro (LC₅₀ = 9.8 ± 1.4 mg·L^–1) and in vivo ((70 ± 5)%). These results demonstrated that compound 33 can be considered as a potential nematicide.     

Novel 1,3,4‐Oxadiazole Derivatives of Dihydropyrimidinones: Synthesis,Anti‐Inflammatory,Anthelmintic, and Antibacterial Activity Evaluation

The present study depicts synthesis of a series of some novel 5‐(5‐(aryl)‐1,3,4‐oxadiazol‐2‐yl)‐3,4‐dihydro‐6‐methyl‐4‐styrylpyrimidin‐2(1H)‐one derivatives. All the newly synthesized compounds were characterized by FTIR, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. The compounds were evaluated for their in vivo anti‐inflammatory activity by the carrageenan‐induced rat paw edema method. The compounds were also screened for their anthelmintic activity on Indian earthworms and antibacterial activity against some gram positive and gram negative strains of bacteria. This pharmacological activity evaluation revealed that, among all the compounds screened, compounds 4b and 4c were found to have promising anti‐inflammatory activity. Interestingly, compounds 4b , 4c , and 4i exhibited appreciable anthelmintic property, while compounds 4c , 4g , and 4h showed leading antibacterial activity against the selected pathogenic strains of bacteria.     

Design,Synthesis, and Herbicidal Evaluation of Novel Uracil Derivatives Containing 1,3,4‐Thiadiazolyl Moiety

Uracil derivatives, such as commercial herbicides butafenacil and benzfendizone, have been identified as inhibitors of protoporphyrinogen oxidase (Protox, EC 1.3.3.4), one of the most important action targets of herbicides. In order to search for novel Protox inhibitors with high efficacy, broad‐spectrum activity, and safety to crops, commercially herbicide butafenacil was used as lead compound for further optimization; a series of title compounds 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h , 8i , 8j , 8k , 8l , 8m , 8n were designed and synthesized by introducing 1,3,4‐thiadiazole moiety into the uracil skeleton. The preliminary bioassays (in vitro) indicated that most of the target compounds displayed better inhibition against Echinochloa crus‐galli than Brassica campestris. The greenhouse bioassay results indicated that most of the compounds tested exhibited good‐to‐excellent herbicidal activities against B. campestris, A. retroflexus, E. crusgalli, and D. sanguinalis in pre‐emergence treatment at a dose of 1500 g/ha, for example, compound 8d showed 100% inhibition against the four plants tested in pre‐emergence treatment at a dose of 1500 g/ha. So, these types of skeletons can be used as valuable lead compounds for the development of a pre‐emergent herbicide.     

Synthesis of Extended 1,3,4‐Oxadiazole and 1,3,4‐Thiadiazole Derivatives in the Suzuki Cross‐coupling Reactions

New derivatives of 1,3,4‐oxadiazole and 1,3,4‐thiadiazole were synthesized by a palladium catalyzed Suzuki cross‐coupling reaction under the conditions of the phase transfer catalysis. The structure of the products, the absorption and emission spectra were also studied.     

Synthesis and Anti‐cancer Activity of 1,3,4‐Thiadiazole and 1,3‐Thiazole Derivatives Having 1,3,4‐Oxadiazole Moiety

Reaction of 1,3,4‐oxadiazolyl‐phenylthiourea 3 with hydrazonoyl halides gave the corresponding 1,3,4‐oxadiazolylimino‐1,3,4‐thiadiazoles. Also, treatment of 3 with ethyl chloroacetate and α‐haloketones afforded the corresponding thiazolidinone and thiazole derivatives, respectively. The structures of the synthesized products were confirmed by spectral data. Ten compounds were evaluated for their anti‐cancer activity against the colon carcinoma cell line (HCT‐116). The results revealed that 1,3,4‐thiadiazole derivatives 13d and 19c (IC₅₀ = 0.73 and 0.86 µg/mL, respectively) have promising antitumor activity against colon carcinoma (HCT‐116), and most of the tested compounds showed moderate anti‐cancer activity.     

Synthesis and Biological Activity of Some Novel Aryl‐Substituted 1,3,4‐Oxadiazole Mannich Bases Containing Pyrimidine Rings

A series of novel Mannich base derivatives (E₁–E₁₅) of 5‐aryl‐1,3,4‐oxadiazole‐2‐thione with substituted pyrimidine were synthesized and characterized by elemental analysis, IR, ¹H‐NMR. The antifungal activities of these compounds were also originally studied. The results showed that most of the title compounds exhibited relatively good fungicidal activities. Especially compounds E₈ and E₁₃ showed better antifungal activity than comparison compound hymexazol. The relationship of structure and activity revealed that the presence of the methyl group at four and six positions of pyrimidine ring remarkably enhanced the antifungal activity of title compounds.     

Synthesis and Insecticidal Evaluation of Novel N‐Pyridylpyrazolecarboxamides Containing Different Substituents in the ortho‐Position

In order to look for novel insecticides containing N‐pyridylpyrazole, ten novel pyrazolecarboxamides containing different ortho‐substituents in the aniline part were synthesized, and their structures were characterized by ¹H NMR, ¹³C NMR and HRMS. The single crystal structure of 10b was determined by X‐ray diffraction. Their evaluated insecticidal activity against oriental armyworm (Mythimna separata) indicated that all the compounds exhibited moderate insecticidal activities.     

含呋喃环双酰肼类衍生物的合成、杀虫活性及3D-QSAR研究

为发现新的昆虫生长调节剂,经单取代苯基呋喃甲酰氯与取代苯甲酰肼反应得到22个未见文献报道的含呋喃环双酰肼类化合物,其结构均通过了IR,1HNMR和元素分析确认.初步生测结果表明,所有目标化合物对豆蚜(Aphisfabae)均有活性,部分目标化合物表现出较好或中等的杀幼虫活性.化合物Ia,Ib和Ic在药剂浓度为0.05%时,对豆蚜的死亡抑制率分别为81.8%,58.4%和52.2%,其中化合物Ia对若蚜的蜕皮和成蚜产雌能力具有一定的抑制作用.而大部分目标化合物在药剂浓度为0.1%,0.05%和0.001%时,对3龄粘虫(Mythimna separate)、棉红蜘蛛(Tetranchus urticae)和尖音淡色库蚊(Culex pipiens pallens)幼虫杀虫活性不明显.采用比较分子力场分析(CoMFA)方法,对22个化合物的杀蚜虫活性进行三维定量构效关系(3D-QSAR)研究.在CoMFA研究中,考察了不同力场和电荷下网格点步长对统计结果的影响.建立了三维定量构效关系CoMFA模型(q2=0.518,r2=0.936).CoMFA模型的立体场、静电场三维等值线图不仅直观地解释了结构与活性的关系,而且为后续优化该系列化合物提供了理论依据.     

Synthesis of New PMB‐Substituted Indoles Containing 1,3,4‐Oxadiazole and 1,2,4‐Triazole Units

A series of new indolyl‐1,3,4‐oxadiazole derivatives 3 , 4 , 5 , 6 , 7 and 10 , indolyl‐1,2,4‐triazole derivatives 14 and 15 was prepared, using 1‐(4‐methoxybenzyl)‐1H‐indole‐3‐carbohydrazide ( 2 ) as a key intermediate. Some of the new compounds were evaluated for their antineoplastic activity.     

Synthesis and Evaluation of 1,3,4‐Thiadiazole Derivatives Containing Cyclopentylpropionamide as Potential Antibacterial Agent

This study aimed to identify new strategies for the control of these plant bacterial diseases by combining a pharmacophoric group of different bioactive compounds. A series of 3‐cyclopentylpropionamide containing 1,3,4‐thiadiazole derivatives was synthesized and characterized via ¹H‐NMR, ¹³C‐NMR, and HRMS. Bioassay results indicated that compounds 7a , 7d , 7j , 7m , 7n , and 7s had excellent antibacterial activity compared with the positive control. Among them, compound 7a exhibited remarkable inhibitory effect against Xoo with an EC₅₀ of 21.41 μg/mL, which surpassed that of thiodiazole copper (67.71 μg/mL) and bismerthiazol (69.05 μg/mL). Greenhouse condition tests further revealed that 7a had approximately equal curative activity and better protection activity (41.58%) against bacterial leaf blight of rice than that of thiodiazole copper and bismerthiazol (46.86 and 42.25%, respectively). Structure–activity relationship analysis exhibited that sulfone fragment favored inhibition. Overall, this study suggested that derivatives containing 1,3,4‐thiadiazole 3‐cyclopentylpropanamide can be used as new lead compounds for bactericide studies.     

Antiviral and Antibacterial Activities of N‐(4‐Substituted phenyl) Acetamide Derivatives Bearing 1,3,4‐Oxadiazole Moiety

In this paper, a series of N‐(4‐substituted phenyl) acetamide derivatives bearing 1,3,4‐oxadiazole moiety were synthesised. Preliminary bioassays revealed that these compounds not only exhibited favourable antiviral activities toward tobacco mosaic virus (TMV) but also demonstrated sustained inhibition activities against plant pathogenic bacteria, including Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri. Among the derivatives, TC ₈ and TC ₂₀ exerted the strongest curative activities against TMV, with half‐maximal effective concentration (EC₅₀) values of 239.5 and 236.2 µg/mL, respectively, which were comparable to that of ningnanmycin (EC₅₀=273.2 µg/mL). Given their simple synthesis, the target compounds can serve as alternative antiviral candidates.     

新型含噁二唑环的苯并噁/噻唑啉酮衍生物的合成、表征及生物活性

以邻氨基苯酚(硫酚)和尿素为起始原料, 经一系列反应, 合成出了30个新型含噁二唑环的苯并噁/噻唑啉酮衍生物(6). 利用IR、¹H NMR 和元素分析对新化合物4 和6 的结构进行了表征. 对所合成的目标化合物进行了抗癌、抗炎和免疫调节活性的筛选, 实验结果表明, 部分目标化合物具有弱的抗癌和免疫调节活性, 对TNF-α 和Cdc25B 磷酸酯酶均无抑制活性.