- Design, Synthesis, and Antifungal Activity of 2,6-Dimethyl-4-aminopyrimidine Hydrazones as PDHc-E1 Inhibitors with a Novel Binding Mode
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A series of novel 2,6-dimethyl-4-aminopyrimidine hydrazones 5 were rationally designed and synthesized as pyruvate dehydrogenase complex E1 (PDHc-E1) inhibitors. Compounds 5 strongly inhibited Escherichia coli (E. coli) PDHc-E1 (IC50 values 0.94-15.80 μM). As revealed by molecular docking, site-directed mutagenesis, enzymatic, and inhibition kinetic analyses, compounds 5 competitively inhibited PDHc-E1 and bound in a "straight"pattern at the E. coli PDHc-E1 active site, which is a new binding mode. In in vitro antifungal assays, most compounds 5 at 50 μg/mL showed more than 80% inhibition against the mycelial growth of six tested phytopathogenic fungi, including Botrytis cinerea, Monilia fructigena, Colletotrichum gloeosporioides, andBotryosphaeria dothidea. Notably, 5f and 5i were 1.8-380 fold more potent against M. fructigena than the commercial fungicides captan and chlorothalonil. In vivo, 5f and 5i controlled the growth of M. fructigena comparably to the commercial fungicide tebuconazole. Thus, 5f and 5i have potential commercial value for the control of peach brown rot caused by M. fructigena.
- Zhou, Yuan,Zhang, Shasha,Cai, Meng,Wang, Kaixing,Feng, Jiangtao,Xie, Dan,Feng, Lingling,Peng, Hao,He, Hongwu
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- Allylic and Allenylic Dearomatization of Indoles Promoted by Graphene Oxide by Covalent Grafting Activation Mode
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The site-selective allylative and allenylative dearomatization of indoles with alcohols was performed under carbocatalytic regime in the presence of graphene oxide (GO, 10 wt percent loading) as the promoter. Metal-free conditions, absence of stoichiometric additive, environmentally friendly conditions (H2O/CH3CN, 55 °C, 6 h), broad substrate scope (33 examples, yield up to 92 percent) and excellent site- and stereoselectivity characterize the present methodology. Moreover, a covalent activation model exerted by GO functionalities was corroborated by spectroscopic, experimental and computational evidences. Recovering and regeneration of the GO catalyst through simple acidic treatment was also documented.
- Lombardi, Lorenzo,Bellini, Daniele,Bottoni, Andrea,Calvaresi, Matteo,Monari, Magda,Kovtun, Alessandro,Palermo, Vincenzo,Melucci, Manuela,Bandini, Marco
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- Design and synthesis of antifungal benzoheterocyclic derivatives by scaffold hopping
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The incidence of invasive fungal infections and associated mortality is increasing dramatically. Although azoles are first-line antifungal agents, cross-resistance and hepatic toxicity are their two major limitations. The discovery of novel non-azole lead compounds will be helpful to overcome these problems. On the basis of our previously reported benzopyran non-azole CYP51 inhibitor, scaffold hopping was used to design structurally diverse new compounds and expand the structure-activity relationships of the lead structure. Five kinds of scaffolds, namely benzimidazole, benzoxazole, benzothiazole, quinazolin-4-one and carboline, were chosen for synthesis. In vitro antifungal activity data and results from molecular docking revealed that the scaffold was important for the antifungal activity. Several compounds showed potent activity against both standard and clinically resistant fungal pathogens, suggesting that they can serve as a good starting point for the discovery of novel antifungal agents.
- Sheng, Chunquan,Che, Xiaoying,Wang, Wenya,Wang, Shengzheng,Cao, Yongbing,Yao, Jianzhong,Miao, Zhenyuan,Zhang, Wannian
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- Synthesis and biological evaluation of (1-aryl-1H-pyrazol-4-yl) (3,4,5-trimethoxyphenyl)methanone derivatives as tubulin inhibitors
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A series of (1-aryl-1H-pyrazol-4-yl) (3,4,5-trimethoxyphenyl)methanones (8a-p, 9a-p) and ketoxime (10c) derivatives were designed and synthesized as antitubulin agents. All of the target compounds were evaluated for the in vitro anti-proliferative activities against three tumor cell lines (A549, HT-1080, SGC-7901). The most promising compounds in this class were (1-(p-tolyl)-1H-pyrazol-4-yl) (3,4,5-trimethoxyphenyl)methanone (9c) and its ketoxime derivative (10c), which significantly inhibited tumor cells growth with IC50 value of 0.054–0.16 μM. Meanwhile, compound 9c exhibited effectively inhibitory activity of tubulin polymerization. Consistent with its antitubulin activity, compound 9c could destructively damage microtubule network and arrest SGC-7901 cell cycle at G2/M phase significantly. The structure-activity relationship (SAR) and conformational analysis indicate that methyl group at C4-position of C-ring is critical for the activities and the amino group at the C5-position of B-ring plays a negative role in maintaining bioactivity. Furthermore, a molecular docking study was performed to elucidate its binding mode at the colchicine site in the tubulin heterodimer.
- Zhai, Min'an,Wang, Long,Liu, Shiyuan,Wang, Lijing,Yan, Peng,Wang, Junfang,Zhang, Jingbo,Guo, Haifei,Guan, Qi,Bao, Kai,Wu, Yingliang,Zhang, Weige
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- Design, synthesis and biological evaluation of tryptamine salicylic acid derivatives as potential antitumor agents
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A series of tryptamine salicylic acid derivatives were synthesized and their antiproliferative activity against MGC-803, MCF-7, HepG2, A549 and HeLa cell lines was evaluated. The structure-activity relationship (SAR) study revealed that different substitutions of the C5 and C3′-C5′ positions have certain effects on the anti-proliferation activity. The growth assay revealed that N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide (E20) showed the most potent and broad-spectrum anticancer inhibition of all the cell lines evaluated, and was only more potent than 5-Fu for the gastric cancer cell line. Preliminary studies indicated that compound E20 could inhibit colony formation and migration of MGC-803 cells. The flow cytometry (FCM) results showed that compound E20 arrested the cell cycle in the G2/M phase and induced apoptosis of MGC-803 cells in a concentration-dependent manner. In addition, the western blot results showed that E20 can down-regulate the expression of hexokinase 2. Our studies suggest that the framework of N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide may be consider as a new type of chemical for designing effective anti-cancer drugs targeting gastric cancer cells.
- Xiong, Runde,He, Dongxiu,Deng, Xiangping,Liu, Juan,Lei, Xiaoyong,Xie, Zhizhong,Cao, Xuan,Chen, Yanming,Peng, Junmei,Tang, Guotao
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- Synthesis and evaluation of indole derivatives as photosynthesis and plant growth inhibitors
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Indole derivatives were synthetized based on the Fischer indole methodology using different phenyl hydrazine hydrochlorides and either cyclohexanone or 2-butanone. The pre- and post-emergent herbicidal activities were evaluated against Ipomoea grandifolia. A carbazole, 6-chloro-2,3,4,9-tetrahydro-1H-carbazole (3b), decreased the PIabs parameter by 32% and increased the cross-section related parameters, indicating the inactivation of the reaction center on photosystem II. Compound 3b acts as a post-emergent herbicide prototype since dry biomass was reduced by 50%, corroborating the fluorescence results. Comparing instead with a germination experiment, 2,3,4,9-tetrahydro-1H-carbazole (3a) was found to be the most effective agent, inhibiting seed germination by 22% and decreasing root length by 50%. The tetrahydrocarbazoles showed better results than indole derivatives potentially due to the presence of methylene groups at structures, which increase the compounds' lipophilicity and may facilitate their access to the plant. In addition, electron withdrawing groups on the aromatic ring were found to correlate with increased herbicide activity. Further optimization of this series towards the development of herbicides is ongoing.
- Mendes, Mylla Cristie Da Silva,Fazolo, Bruno Rodrigues,De Souza, Jéssica Maria,De Vasconcelos, Leonardo Gomes,De Sousa Junior, Paulo Teixeira,Dall'Oglio, Evandro Luiz,Soares, Marcos Ant?nio,Sampaio, Olívia Moreira,Vieira, Lucas Campos Curcino
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- Synthesis, in vitro Antimicrobial, and Cytotoxic Activities of New 1,3,4-Oxadiazin-5(6H)-one Derivatives from Dehydroabietic Acid
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A series of new 1,3,4-oxadiazin-5(6H)-one derivatives (6a–n) of dehydroabietic acid were designed and synthesized as potential antimicrobial and antitumor agents. Their structures were characterized by IR, 1H NMR, 13C NMR, MS, and elemental analyses. All the title compounds were evaluated for their antimicrobial activity against four bacterial and three fungal strains using the serial dilution method. Among them, compound 6e showed the highest antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) value of 1.9 μg/mL. In addition, the in vitro cytotoxic activities of the title compounds were also assayed against three human carcinoma cell lines (MCF-7, SMMC-7721, and HeLa) through the MTT colorimetric method. As a result, compounds 6b, 6g, 6k, and 6m exhibited significant inhibition against at least one cell line with IC50 values below 10 μM. Compound 6m was especially found to be the most potent derivative with IC50 values of 2.26 ± 0.23, 0.97 ± 0.11, and 1.89 ± 0.31 μM against MCF-7, SMMC-7721, and HeLa cells, respectively, comparable to positive control etoposide.
- Jin, Xiao-Yan,Zhang, Kang-Ping,Chen, Hao,Miao, Ting-Ting,Wang, Shi-Fa,Gu, Wen
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- A diversity-oriented approach to indolocarbazoles: Via Fischer indolization and olefin metathesis: Total synthesis of tjipanazole D and i
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New synthetic strategies to indolocarbazoles have been reported via two-fold Fischer indolization under green conditions using l-(+)-tartaric acid and N,N-dimethyl urea. Starting with cyclohexanone, a bench-top starting material, this methodology has been extended to the total synthesis of natural products such as tjipanazoles D and I as well as the core structure of asteropusazole and racemosin B. Here, atom economical reactions like ring-closing metathesis, enyne-metathesis, and the Diels-Alder reaction have been used as key steps. Diverse strategies demonstrated here are useful in medicinal chemistry and materials science to design a library of decorated indoles.
- Kotha, Sambasivarao,Saifuddin, Mohammad,Aswar, Vikas R.
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- Synthesis method of metolachlor intermediate
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The synthesis method comprises the following steps: S1) nitration reaction of chlorobenzene in a nitration reagent to obtain a mixture of o-chloronitrobenzene and p-chloronitrobenzene without separation. S2) The mixture of o-chloronitrobenzene and p-chloronitrobenzene is subjected to catalytic hydrogenation reaction to obtain the mixture of o-chloroaniline and p-chloroaniline, and the product does not need to be separated. S3) The mixture of o-chloroaniline and chloroaniline is subjected to diazotization reaction to obtain the mixture of o-chlorophenylhydrazine and p-chlorophenylhydrazine, and the product does not need to be separated. S4) The mixture of o-chlorophenylhydrazine and p-chlorophenylhydrazine and aldehyde are subjected to a condensation reaction to obtain a triazole ring mixture of Formulae I through a and I through b. S5) The triazole ring mixture is subjected to chlorination reaction to obtain the metolachlor intermediate shown in the formula I. 2, 4 - Dichloroaniline is used as a raw material, the production cost of the metolachlor is reduced, and the supply limitation of the raw material is avoided.
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Paragraph 0078-0088; 0097-0107
(2021/09/21)
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- Synthesis and evaluation of aryl substituted propyl piperazines for potential atypical antipsychotic activity
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Background: Schizophrenia is a disorder with complex etiology with hyperdopaminer-gia as the leading underlying cause. Atypical antipsychotics are the agents which do not give rise to significant extrapyramidal side effects and are more effective against negative symptoms of schizophrenia. Introduction: A new series of chloro-substituted substituted aryloxypiperazine derivatives and their indole based derivatives was designed and evaluated for atypical antipsychotic activity based on established models for combined dopaminergic and serotonergic antagonism. Method: The present series of compounds were designed based on 3D similarity studies, synthesized and evaluated for atypical antipsychotic activity in animal models for combined dopaminer-gic and serotonergic antagonism. The blood-brain barrier penetration potential was assessed from theoretical log BB values computed through an online software program. Results: Theoretical ADME profiling of the designed compounds based on selected physicochem-ical parameters suggested excellent compliance with Lipinski’s rules. The log BB values obtained for the compounds suggested a good potential for brain permeation. Indole substitution contributed towards an improved efficacy over aryloxy analogs. Lead compounds showed a potential for combined dopaminergic and serotonergic antagonism. Conclusion: The 5-methoxy indole based compounds 16 and 17 were identified as the lead compounds displaying a potential atypical antipsychotic profile.
- Singh, Shalu,Bali, Alka,Peshin, Tania
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p. 429 - 441
(2021/03/26)
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- Synthesis process of p-chlorophenylhydrazine hydrochloride
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The invention relates to the technical field of organic synthesis, in particular to a synthesis process of p-chlorophenylhydrazine hydrochloride. The synthesis process comprises the following steps: (1) diazotization: mixing p-chloroaniline, strong acid and water, and adding a nitrite solution to obtain a substance A; and (2) catalytic hydrogenation: mixing the substance A with a catalyst under ahydrogen condition, and filtering the liquid to obtain the product. The process provided by the invention has the advantages of high yield and purity, environmental protection and simple operation.
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Paragraph 0064-0092
(2019/10/29)
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- Preparation method for high-purity pyraclostrobin
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The invention relates to the technical field of compound synthesis, in particular to a preparation method for high-purity pyraclostrobin. The pyraclostrobin is synthesized from p-chloroaniline and o-nitrosotoluene as initial raw materials through the steps of diazotizing, cyclizing, oxidizing, bromizing, condensating, reducing, acylating, methylating and the like. According to the preparation method, the problem that the purity of the pyraclostrobin in the prior art is low is solved; and the preparation method for the pyraclostrobin has the advantages of high yield, high purity and high material utilization rate.
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Paragraph 0029; 0053; 0065-0066
(2019/04/02)
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- Discovery of 1,3,4-oxadiazol-2-one-containing benzamide derivatives targeting FtsZ as highly potent agents of killing a variety of MDR bacteria strains
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The spread of infections caused by multidrug-resistant (MDR) pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), has created a need for new antibiotics with novel mechanisms of action. The bacterial division protein FtsZ has been identified as a novel drug target that can be exploited clinically. As part of an ongoing effort to develop FtsZ-targeting antibacterial agents, we describe herein the design, synthesis and bioactivity of six series of novel 1,3,4-oxadiazol-2-one-containing, 1,2,4-triazol-3-one-containing and pyrazolin-5-one-containing benzamide derivatives. Among them, compound A14 was found to be the most potent antibacterial agent, much better than clinical drugs such as ciprofloxacin, linezolid and erythromycin against all the tested gram-positive strains, particularly methicillin-resistant, penicillin-resistant and clinical isolated S. aureus. Subsequent studies on biological activities and docking analyses proved that A14 functioned as an effective compound targeting FtsZ. Preliminary SAR indicated a general direction for further optimization of these novel analogues. Taken together, this research provides a promising chemotype for developing newer FtsZ-targeting bactericidal agents.
- Bi, Fangchao,Song, Di,Qin, Yinhui,Liu, Xingbang,Teng, Yuetai,Zhang, Na,Zhang, Panpan,Zhang, Nan,Ma, Shutao
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p. 3179 - 3193
(2019/06/17)
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- Synthesis of Aryl Hydrazines via CuI/BMPO Catalyzed Cross-Coupling of Aryl Halides with Hydrazine Hydrate in Water
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The N,N’-bis(2,6-dimethylphenyl)oxalamide was discovered as a powerful ligand for Cu-catalyzed cross-coupling of aryl halides with hydrazine hydrate, leading to the formation of a variety of aryl hydrazines at 80 oC in water under the assistance of K3PO4 and 4 mol% cetyltrimethylammonium bromide from aryl bromides and aryl iodides. Good to excellent yields were observed in most cases.
- Kumar, Siripuram Vijay,Ma, Dawei
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supporting information
p. 1003 - 1006
(2018/09/20)
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- Indolamide compound with anti-tumor activity
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The invention discloses an indolamide compound with anti-tumor activity, which can be used for treating cancers, particularly gastric cancer, liver cancer, breast cancer, lung cancer cells and cervical cancer, and is particularly used for inhibiting human gastric cancer cells MGC-803, human liver cancer cells HepG2, human breast cancer cells MCF-7, human lung cancer cells A549 and human cervical cancer cell HELA cell strain. Therefore, the indolamide compound with anti-tumor activity can be used as a broad-spectrum anti-tumor drug, and has a good development and application prospect.
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Paragraph 0039-0042
(2019/01/07)
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- Method for synthesizing p-chlorophenyluhydrazine hydrochloride as fungicide precursor
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The invention discloses a method for synthesizing p-chlorophenyluhydrazine hydrochloride as a fungicide precursor. The method comprises the following steps: taking diazonium chloride p-chlorobenzenethiol as a raw material; carrying out catalyzed hydrogeneration reduction in a fixed bed reactor to obtain a product; cooling, crystallizing, filtering and discharging the product, and drying to obtain the finished product. According to the method, the p-chlorophenyluhydrazine hydrochloride as the fungicide precursor is obtained by taking the diazonium chloride p-chlorobenzenethiol as the raw material, and carrying out low-temperature catalyzed hydrogeneration reduction reaction in the tubular reactor. The process is simple to operate, the steps are carried out orderly, the amounts of waste gas, waste water and solid wastes are small, production is clean, and the method is safe and environmentally friendly. The tubular reactor is adopted, by-products can be rapidly separated from products, yield of products is improved, meanwhile, continuous operation is realized, dangerousness in an industrial process is avoided, and potential safety hazards are eliminated.
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Paragraph 0017; 0018; 0019; 0020; 0021; 0022; 0023
(2017/04/28)
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- Rh(II)-catalyzed intramolecular annulation of N-sulfonyl 1,2,3-triazoles with indole derivatives: A new method for synthesis pyranoindoles
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A direct and highly stereoselective approach for the synthesis of Z-alkenyl-pyranoindoles had been developed by utilizing Rh(II)-catalyzed intramolecular cyclization of N-sulfonyl-1,2,3-triazoles with indole derivatives. A variety of pyranoindoles were obtained in 44-93% yields. Moreover, a more convenient synthesis of pyranoindoles starting from terminal alkyne was realized via a Cu-Rh sequentially catalyzed one-pot cascade reaction.
- Xie, Hui,Yang, Jian-Xin,Bora, Pranjal Protim,Kang, Qiang
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supporting information
p. 3014 - 3021
(2016/05/19)
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- Method for synthesizing pyraclostrobin intermediate 1-(4-chlorophenyl)-3-hydroxy-1-h-pyrazole
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The invention discloses a method for synthesizing a pyraclostrobin intermediate 1-(4-chlorophenyl)-3-hydroxy-1-h-pyrazole. The method comprises the steps that p-bromochlorobenzene and hydrazine hydrate are used as reaction raw materials, a phase transfer catalyst, a solvent and a catalyst are added for a reaction, and p-chlorobenzene hydrazine hydrochloride is prepared; the p-chlorobenzene hydrazine hydrochloride reacts with alkali, sodium alkoxide and acrylate, and a toluene solution of an intermediate pyrazolone is prepared in the presence of toluene; toluene in the toluene solution is removed, alkali and hydrogen peroxide are added for oxidization, and the 1-(4-chlorophenyl)-3-hydroxy-1-h-pyrazole solution is prepared. According to the synthesizing method, p-bromochlorobenzene and hydrazine hydrate are reacted for preparing the p-chlorobenzene hydrazine hydrochloride, so that the amount of wastewater produced in the synthesis process can be greatly reduced, usage of sulfite reducing agent and a large amount of acid is avoided, hazardous substance is prevented from being produced in the whole technological process, environment-friendly production is achieved, the HPLC content of 1-(4-chlorophenyl)-3-hydroxy-1-h-pyrazole is larger than or equal to 98%, and the yield is larger than or equal to 90%.
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Paragraph 0030-0054; 0055-0059; 0060-0069
(2018/02/04)
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- Synthetic method for 4-chlorophenylhydrazine hydrochloride
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The invention discloses a synthetic method for 4-chlorophenylhydrazine hydrochloride. The synthetic method comprises the following steps: 4-bromochlorobenzene and hydrazine hydrate are taken as reaction raw materials, and a phase transfer catalyst, a solvent and a catalyst are added for a reaction; after the reaction, solids are filtered and separated, and a solvent is removed from a filtrate through distillation; hydrochloric acid is added to residues obtained after distillation, and the mixture is stirred and filtered; filter residues are washed with water and dried, and 4-chlorophenylhydrazine hydrochloride is obtained. The synthetic method aims to solve the problem of generation of a large amount of wastewater due to adoption of a current commonly used method for reduction acidification after diazotization of 4-chloroaniline, 4-bromochlorobenzene and hydrazine hydrate are taken as the reaction raw materials, the phase transfer catalyst, the solvent and the catalyst are added for the reaction, the reaction steps are simple, the wastewater produced in a 4-chlorophenylhydrazine synthetic method is reduced remarkably, sulfur dioxide is prevented from being produced through reduction of sodium sulfite, excessive hydrazine hydrate and solvent can be recovered and reused after reaction, and the method is environment-friendly.
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Paragraph 0055; 0056; 0057; 0058; 0059
(2017/06/02)
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- Rhodium(III)-catalyzed in situ oxidizing directing group- assisted c-h bond activation and olefination: A route to 2-vinylanilines
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A new and efficient method for the synthesis of 2-vinylanilines from the reaction of arylhydrazine hydrochlorides with alkenes and diethyl ketone via a rhodium-catalyzed C-H activation is described. The oxidant-free olefination reaction involves the in situ generation of an -N-N=CR1R2 moiety as the oxidizing directing group thus providing an easy access to 2-vinylanilines.
- Muralirajan, Krishnamoorthy,Haridharan, Radhakrishnan,Prakash, Sekar,Cheng, Chien-Hong
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supporting information
p. 761 - 766
(2015/03/18)
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- Synthesis, fungicidal activity, structure-activity relationship and density functional theory studies of novel oxime ether derivatives containing 1-aryl-3-oxypyrazoles
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A series of 16 oxime ether derivatives containing 1-aryl-3-oxypyrazoles were synthesised, and the structure of one of them, (E)-methyl 2-(2-({(1-(4-chlorophenyl)-1H-pyrazol-3-yl)-oxy}methyl)phenyl)-2-(methoxyimino)acetate was determined by X-ray diffraction crystallography. Preliminary bioassays indicated that some of these compounds exhibited very good fungicidal activities against Rhizoctonia solani, especially the ester 2-(2-({(1-(4-chlorophenyl)-1H-pyrazol-3-yl)-oxy}methyl)phenyl)-2-(methoxyimino)acetate, which displayed greater activity than control compound pyraclostrobin at a dosage of 0.1 μg mL-1. The relationship between structure and fungicidal activity was discussed. Density functional theory studies of the 3-methyl heterocyclic ester and the 4-chorophenyl heterocyclic N-methylamide were carried out and the results discussed in terms of the wide difference in fungicidal activity shown by each compound.
- Lv, Kunzhi,Liu, Yuanyuan,Li, Yi,Xu, Guanghui,Pan, Xuechun,Li, Fangshi,Chen, Kai,Huang, Bin,Yang, Yaping
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p. 594 - 600
(2015/11/27)
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- Facile and convenient synthesis of aryl hydrazines via copper-catalyzed C-N cross-coupling of aryl halides and hydrazine hydrate
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An efficient and convenient method for the synthesis of aryl hydrazines has been developed via copper-catalyzed cross-coupling of aryl bromides and hydrazine with a readily accessible ligand and water as a solvent. The multigram scale procedure is applicable to aryl bromides bearing both moderately electron-donating and electron-withdrawing substituents in the aromatic nucleus. No column chromatography is required to obtain aryl hydrazine hydrochlorides in good yields.
- Kurandina, Daria V.,Eliseenkov, Eugene V.,Ilyin, Petr V.,Boyarskiy, Vadim P.
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p. 4043 - 4048
(2014/06/09)
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- Design, synthesis, crystal structures, and insecticidal activities of eight-membered azabridge neonicotinoid analogues
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Three series of novel azabridge neonicotinoid analogues were designed and synthesized, which were constructed by starting material A, glutaraldehyde, and primary amine hydrochlorides (aliphatic amines, phenylhydrazines, and anilines). Most of the eight-membered azabridge compounds presented higher insecticidal activities than oxabridged compound B against cowpea aphid (Aphis craccivora) and brown planthopper (Nilaparvata lugens). Compared with imidacloprid, some azabridged compounds exhibited excellent insecticidal activity against brown planthopper. The crystal structures and bioassay indicated that changing bridge atoms from O to N could lead to entirely different conformations, which might be the important influential factor of the bioactivities.
- Xu, Renbo,Xia, Rui,Luo, Ming,Xu, Xiaoyong,Cheng, Jiagao,Shao, Xusheng,Li, Zhong
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p. 381 - 390
(2014/02/14)
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- Discovery of lead compounds targeting the bacterial sliding clamp using a fragment-based approach
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The bacterial sliding clamp (SC), also known as the DNA polymerase III β subunit, is an emerging antibacterial target that plays a central role in DNA replication, serving as a protein-protein interaction hub with a common binding pocket to recognize linear motifs in the partner proteins. Here, fragment-based screening using X-ray crystallography produced four hits bound in the linear-motif-binding pocket of the Escherichia coli SC. Compounds structurally related to the hits were identified that inhibited the E. coli SC and SC-mediated DNA replication in vitro. A tetrahydrocarbazole derivative emerged as a promising lead whose methyl and ethyl ester prodrug forms showed minimum inhibitory concentrations in the range of 21-43 μg/mL against representative Gram-negative and Gram-positive bacteria species. The work demonstrates the utility of a fragment-based approach for identifying bacterial sliding clamp inhibitors as lead compounds with broad-spectrum antibacterial activity.
- Yin, Zhou,Whittell, Louise R.,Wang, Yao,Jergic, Slobodan,Liu, Michael,Harry, Elizabeth J.,Dixon, Nicholas E.,Beck, Jennifer L.,Kelso, Michael J.,Oakley, Aaron J.
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supporting information
p. 2799 - 2806
(2014/04/17)
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- Regioselective synthesis of indoles via rhodium-catalyzed C-H activation directed by an in-situ generated redox-neutral group
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A regioselective synthesis of indoles from arylhydrazine hydrochlorides with alkynes and diethyl ketone catalyzed by a rhodium complex is described. A possible mechanism involving an in-situ generated oxidizing directing group -N-Ni'CR1R2 assisted ortho-C-H activation and reductive elimination are proposed. The catalytic reaction is highly compatible with a wide range of functional arylhydrazines and alkynes. The reaction proceeds under mild reaction conditions and is atom-step economical.
- Muralirajan, Krishnamoorthy,Cheng, Chien-Hong
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p. 1571 - 1576
(2014/06/09)
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- Design, synthesis and pharmacological evaluation of 6,7-disubstituted-4- phenoxyquinoline derivatives as potential antitumor agents
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Two series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 2,4-imidazolinedione/pyrazolone scaffold were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against HT-29, H460, A549, MKN-45, and U87MG cancer cell lines in vitro. The pharmacological data indicated that most of the tested compounds showed moderate to significant cytotoxicity and high selectivity against HT-29, H460 and A549 cancer cell lines as compared with foretinib. The SAR analyses indicated that compounds with halogen groups, especially trifluoromethyl groups at 2-position on the phenyl ring (moiety B) were more effective. In this study, a promising compound 17 (c-Met IC50 = 2.20 nM, a multi-target tyrosine kinase inhibitor) showed the most potent antitumor activities with IC50 values of 0.14 μM, 0.18 μM, 0.09 μM, 0.03 μM, and 1.06 μM against HT-29, H460, A549, MKN-45, and U87MG cell lines, respectively.
- Zhou, Shunguang,Ren, Jianguo,Liu, Mingmei,Ren, Lixiang,Liu, Yajing,Gong, Ping
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- Design, synthesis and pharmacological evaluation of 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents
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Two series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 2,4-imidazolinedione/pyrazolone scaffold were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against HT-29, H460, A549, MKN-45, and U87MG cancer cell lines in vitro. The pharmacological data indicated that most of the tested compounds showed moderate to significant cytotoxicity and high selectivity against HT-29, H460 and A549 cancer cell lines as compared with foretinib. The SAR analyses indicated that compounds with halogen groups, especially trifluoromethyl groups at 2-position on the phenyl ring (moiety B) were more effective. In this study, a promising compound 17 (c-Met IC50= 2.20 nM, a multi-target tyrosine kinase inhibitor) showed the most potent antitumor activities with IC50values of 0.14 μM, 0.18 μM, 0.09 μM, 0.03 μM, and 1.06 μM against HT-29, H460, A549, MKN-45, and U87MG cell lines, respectively.
- Zhou, Shunguang,Ren, Jianguo,Liu, Mingmei,Ren, Lixiang,Liu, Yajing,Gong, Ping
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- Indole synthesis by rhodium(III)-catalyzed hydrazine-directed C-H activation: Redox-neutral and traceless by N-N bond cleavage
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Fishing for complements! There is an alternative to the useful Fischer indole synthesis. The new method utilizes the same retrosynthetic disconnection but is based on a RhIII-catalyzed directed C-H activation step and a successive coupling with alkynes. Copyright
- Zhao, Dongbing,Shi, Zhuangzhi,Glorius, Frank
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supporting information
p. 12426 - 12429
(2013/12/04)
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- Design, synthesis and biological activities of novel benzoyl hydrazines containing pyrazole
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In search of environmentally benign compounds with high biological activity, low toxicity and low resistance, 8 novel benzoyl hydrazines containing pyrazole were designed and synthesized. All compounds were characterized by 1H NMR spectra and HRMS. The preliminary results of biological activity assessment indicated that most of title compounds exhibited certain insecticidal activities against Mythimna separata Walker at 200 mg·L -1 but excellent fungicidal activities against six fungus at 50 mg·L-1, which were better than the control. Eight novel benzoyl hydrazines containing pyrazole were designed and synthesized. The preliminary results of biological activity assessment indicated that most of title compounds exhibited certain insecticidal activities against Mythimna separata Walker at 200 mg·L-1 but excellent fungicidal activities against six fungus at 50 mg·L-1, which were better than the control. Copyright
- Yan, Tao,Yu, Shujing,Liu, Pengfei,Liu, Zhuo,Wang, Baolei,Xiong, Lixia,Li, Zhengming
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experimental part
p. 919 - 923
(2012/06/01)
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- Piecing together the puzzle: Understanding a mild, metal free reduction method for the large scale synthesis of hydrazines
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A key intermediate for the synthesis of hydrazines via a mild, metal free reduction of diazonium salts has been isolated and characterized by X-ray analysis. The presence of this intermediate is general, as demonstrated by the preparation of a number of analogues. A discussion of the mechanism and potential benefits of such a process are also described.
- Browne, Duncan L.,Baxendale, Ian R.,Ley, Steven V.
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supporting information; experimental part
p. 10296 - 10303
(2012/01/04)
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- Synthesis and anti-tumor activity of 2-amino-3-cyano-6-(1H-indol-3-yl)-4- phenylpyridine derivatives in vitro
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A series of novel 2-amino-3-cyano-6-(1H-indol-3-yl)-4-phenylpyridine derivatives were synthesized and their cytotoxic activity against A549, H460, HT-29 and SMMC-7721 cell lines was evaluated in vitro. Among them, ten compounds (10, 11, 14, 16, 17, 26, 27, 29, 30 and 31) displayed excellent anti-tumor activity against different cell lines. The most promising compound 27 showed strong anti-tumor activity against A549, H460, HT-29 and SMMC-7721 cell lines with IC50 values of 22, 0.23, 0.65 and 0.77 nM, which were 2.6-, 83-, 1.1 × 103- and 2.0 × 103- fold more active than MX-58151 (IC50 values of 0.058, 0.019, 0.70 and 1.53 μM), respectively.
- Zhang, Fan,Zhao, Yanfang,Sun, Li,Ding, Lu,Gu, Yucheng,Gong, Ping
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experimental part
p. 3149 - 3157
(2011/06/26)
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- Copper-mediated synthesis of substituted 2-aryl-N-benzylbenzimidazoles and 2-arylbenzoxazoles via C-H functionalization/C-N/C-O bond formation
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An efficient method for the transformation of N-benzyl bisarylhydrazones and bisaryloxime ethers to functionalized 2-aryl-N-benzylbenzimidazoles and 2-arylbenzoxazoles is described. The protocol involves a copper(II)-mediated cascade C-H functionalization/C-N/C-O bond formation under neutral conditions. Substrates having either electron-donating or -withdrawing substituents undergo the cyclization to afford the target heterocycles at moderate temperature.
- Guru, Murali Mohan,Ali, Md Ashif,Punniyamurthy, Tharmalingam
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scheme or table
p. 5295 - 5308
(2011/08/05)
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- Synthesis and antimicrobial activities of novel 1H-dibenzo[a,c]carbazoles from dehydroabietic acid
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A series of novel 1H-dibenzo[a,c]carbazole derivatives were synthesized in good yield through reaction of methyl 7-oxo-dehydroabietate with a variety of substituted phenylhydrazines. The structures of the newly synthesized compounds were confirmed by IR, 1H NMR, MS spectral studies and elemental analysis. All compounds were investigated for their activity against four bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas fluorescens) and three fungi (Trichophyton rubrum, Candida albicans and Aspergillus niger). Among the compound tested, 6d, 6e, 6f and 6m exhibited pronounced antibacterial activities and 6e and 6m also showed moderate antifungal activities. Particularly, 6d exhibited stronger antibacterial activity against B. subtilis comparable to positive control.
- Gu, Wen,Wang, Shifa
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experimental part
p. 4692 - 4696
(2010/10/03)
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- Synthesis, crystal structure and fungicidal activities of new type oxazolidinone-based strobilurin analogues
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A series of oxazolidinone-based strobilurin analogues were efficiently synthesized by the reaction of 3-(2-bromomethylphenyl) oxazolidin-2-one with 1-substituted phenyl-2H-pyrazolin-3-one. Their structures were confirmed and characterized by 1H-NMR, 13C-NMR, elemental analysis, and mass spectroscopy. In addition, the crystal structure of the target compound 3-(2-((1-phenyl-2H-pyrazol-3-yloxy)methyl)phenyl) oxazolidin-2-one was determined by single crystal X-ray diffraction. The bioassay results of these compounds indicated that some of the oxazolidin-2-one derivatives containing N-substituted phenyl 2H-pyrazol ring exhibited potential in vivo fungicidal activities against M. grisea at the dosage of 1 g L-1.
- Li, Yuhao,Liu, Rui,Yan, Zhangwei,Zhang, Xiangning,Zhu, Hongjun
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experimental part
p. 3341 - 3347
(2012/05/05)
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- New Heterocyclic compounds for therapeutic use
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A class of compounds particularly diaryl pyrazole of general formulas 1 and 2 where R and R′ represents alkyl, hydrogen, halogens, haloalkyl, cyano, nitro, formyl, carboxyl, alkoxycarbonyl, carboxyalkyl, alkoxycarbonylalkyl, hydroxyalkyl, alkylthio, alkylsulfinyl, alkylsulphonyl, N- alkylsulfamyl, N-arylsulfamyl, cyanoamido, amino, amidino, N-monoalkylamido, N-monoarylamido, N,N-dialkylamido, N-alkyl-N-arylamido, N, N-dialkylsulfamyl with the alkyl, or alkyl part of each such group containing 1-3 carbon atoms or mixtures thereof optionally their salts when they exist, and preparation thereof. The compounds of the present invention are antiinflammatory, antipyretic, antirheumatic, antiosteoarthritic agents with antibacterial activity. The particular class of compounds is given below (Formula 1 and Formula 2).
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- Syntheses of 4-(5-oxo-1,2,4-triazol-3-yl)-sydnones and 4(4-arylamino-5-oxo-1,2,4-triazol-3-yl)-sydnones from sydnone derivatives and their fragments
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4-(5-oxo-1,2,4-triazol-3-yl)-sydnones 11 and 4-(4-arylamino-5-oxo-1,2,4-triazol-3-yl)-sydnones 13 have been obtained from a-chloroformylarylhydrazine hydrochloride 2. Moreover, the intermediates, including 3, 4, 9 and 10, in this study are synthetically informative and valuable. It is also noteworthy that three reactants, 1, 2 and sydnonecarbaldehydes, were prepared from sydnone derivatives and their fragments. The oxidative cyclizations of sydnonecarbaldehyde semicarbazones 9 and carbazpnes 10 with two different oxidizing agents (Cu(ClO4)2 and Fe(ClO4)3) have been extensively examined. The reaction time and the yields of cyclizations were affected by the substituents of semicarbazones 9 and carbazones 10.
- Kuo,Lee,Yeh
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p. 227 - 240
(2007/10/03)
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- Syntheses of α-Haloformylarylhydrazines and Their Self-dimerizations
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α-Haloformylarylhydrazine hydrohalides 1 were prepared through ring opening of 3-aryl-4-halosydnones 7 with hydrohalic acids in EtOAc in moderate yields.Reactions between compounds 1 and primary alcohols gave alkyl 1-arylhydrazinecarboxylates 12 and 14, important intermediates in syntheses of antiinflammatory drugs.Compounds, 16, 4-aryl-2-(arylhydrazin-1-yl)-1,3,4-oxadiazolin-5-ones, and compounds 18, 1,4-diaryl-1,4-dihydro-1,2,4,5-tetrazine-3,6-(2H,5H)-diones, were synthesized by self-dimerization of compounds 1.Compounds 18 were also converted to compounds 17 via intramolecular rearrangement.Structural elucidation and verification of the reaction mechanisms are presented.Key Words 3-Aryl-4-halosydnone; α-Haloformylarylhydrazine hydrohalide; Acid hydrolysis; Self-dimerization; Intramolecular rearrangement.
- Kuo, C. N.,Wu, M. H.,Chen, S. P.,Li, T. P.,Huang, C. Y.,Yeh, M. Y.
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p. 849 - 856
(2007/10/03)
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- Lipoxygenase Inhibitors, III: Synthesis of Tetrahydrobenzazepinone Phenylhydrazones
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Tetrahydro-2H-benzazepin-2-ones as starting substances are synthesized by Beckmann rearrangement or Schmidt reaction.The tetrahydrobenzazepinones are transformed into the thiones, thiolactim ethers and phenylhydrazones.The compounds are tested as inhibitors of soja lipoxygenase.
- Buege, Axel,Locke, Christian,Koehler, Thomas,Nuhn, Peter
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