2900-63-2Relevant articles and documents
Aromatic acyl hydrazone derivative and application thereof as NA inhibitor
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Paragraph 0039; 0044-0046; 0258-0262, (2020/12/30)
The invention relates to an aromatic acyl hydrazone derivative as shown in a structural formula I, pharmaceutically acceptable salt and a pharmaceutical composition thereof, and application of the aromatic acyl hydrazone derivative and the pharmaceutically acceptable salt and the pharmaceutical composition in preparation of an influenza virus neuraminidase inhibitor, wherein R is one of trifluoromethyl, nitryl, 3-methyl-4-nitryl, 3-hydroxyl-4-nitryl, 3-nitryl-4-hydroxyl, hydroxyl, dihydroxyl, dinitryl, 3-methoxy-4-hydroxyl or trihydroxyl; Y is selected from hydroxyl, dihydroxyl, 2-hydroxyl-3-methoxy, 2-hydroxyl-4-methoxy,2-hydroxyl-5-methoxy,2-hydroxyl-6-methoxy,3-hydroxyl-2-methoxy,3-hydroxyl-4-methoxy,3-hydroxyl-5-methoxy,3-hydroxyl-6-methoxy,4-hydroxyl-2-methoxy,4-hydroxyl-3-methoxy,4-hydroxyl-3,5-dimethoxy, trihydroxyl, 4-hydroxyl-3-ethoxy, or 4-hydroxyl-3,5-dimethoxy; w is selected from CH or N; and z is selected from CH or N.
Synthesis and antimicrobial activity of piperine analogues containing 1,2,4-triazole ring
Kumar, Kottakki Naveen,Amperayani, Karteek Rao,Ummdi, V. Ravi Sankar,Parimi, Uma Devi
, p. 1077 - 1080 (2019/04/05)
A series 1,2,4-triazole piperine analogues (TP1-TP6) were designed and synthesized. The structures were confirmed using 1H NMR and 13C NMR. Antibacterial study was done using Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative microorganisms (E. coli and Pseudomonas aeruginosa) by disc diffusion method. Compound containing chloro substitution (TP6) showed the highest effect, while compound TP1, TP3, TP4, TP5 showed the moderate activity.
Structural design, synthesis and substituent effect of hydrazone-N-acylhydrazones reveal potent immunomodulatory agents
Meira, Cássio S.,dos Santos Filho, José Maurício,Sousa, Caroline C.,Anjos, Pamela S.,Cerqueira, Jéssica V.,Dias Neto, Humberto A.,da Silveira, Rafael G.,Russo, Helena M.,Wolfender, Jean-Luc,Queiroz, Emerson F.,Moreira, Diogo R.M.,Soares, Milena B.P.
, p. 1971 - 1985 (2018/03/12)
4-(Nitrophenyl)hydrazone derivatives of N-acylhydrazone were synthesized and screened for suppress lymphocyte proliferation and nitrite inhibition in macrophages. Compared to an unsubstituted N-acylhydrazone, active compounds were identified within initial series when hydroxyl, chloride and nitro substituents were employed. Structure-activity relationship was further developed by varying the position of these substituents as well as attaching structurally-related substituents. Changing substituent position revealed a more promising compound series of anti-inflammatory agents. In contrast, an N-methyl group appended to the 4-(nitrophenyl)hydrazone moiety reduced activity. Anti-inflammatory activity of compounds is achieved by modulating IL-1β secretion and prostaglandin E2 synthesis in macrophages and by inhibiting calcineurin phosphatase activity in lymphocytes. Compound SintMed65 was advanced into an acute model of peritonitis in mice, where it inhibited the neutrophil infiltration after being orally administered. In summary, we demonstrated in great details the structural requirements and the underlying mechanism for anti-inflammatory activity of a new family of hydrazone-N-acylhydrazone, which may represent a valuable medicinal chemistry direction for the anti-inflammatory drug development in general.
N-(5-Methyl-1,3-Thiazol-2-yl)-2-{[5-((Un)Substituted- Phenyl)1,3,4-Oxadiazol-2-yl]Sulfanyl}acetamides. Unique Biheterocycles as Promising Therapeutic Agents
Abbasi,Ramzan,Aziz-ur-Rehman,Siddiqui,Shah,Hassan,Seo,Ashraf,Mirza,Ismail
, p. 801 - 811 (2019/02/27)
An electrophile, 2-bromo-N-(5-methyl-1,3-thiazol-2-yl)acetamide, was synthesized by the reaction of 5-methyl-1,3-thiazol-2-amine and bromoacetyl bromide in an aqueous medium. In a parallel scheme, a series of (un)substituted benzoic acids was converted sequentially into respective esters, acid hydrazides, and then into 1,3,4-oxadiazole heterocyclic cores. The electrophile was coupled with the aforementioned 1,3,4-oxadiazoles to obtain the targeted bi-heterocyles. Structural analysis of the synthesized compounds was performed by IR, EI-MS, 1H NMR, and 13C NMR. The enzyme inhibition study of these molecules was carried out against four enzymes, namely, acetylcholinesterase, butyrylcholinesterase, α-glucosidase, and urease. The interactions of these compounds with respective enzymes were recognized by their in silico study. Moreover, their cytotoxicity was also determined to find out their utility as possible therapeutic agents.
S-substituted 3,5-dinitrophenyl 1,3,4-oxadiazole-2-thiols and tetrazole-5-thiols as highly efficient antitubercular agents
Karabanovich, Galina,Něme?ek, Jan,Valá?ková, Lenka,Carazo, Alejandro,Kone?ná, Klára,Stola?íková, Ji?ina,Hrabálek, Alexandr,Pavli?, Oto,Pávek, Petr,Vávrová, Kate?ina,Roh, Jaroslav,Klime?ová, Věra
, p. 369 - 383 (2016/12/22)
Two new classes of antitubercular agents, namely 5-alkylsulfanyl-1-(3,5-dinitrophenyl)-1H-tetrazoles and 2-alkylsulfanyl-5-(3,5-dinitrophenyl)-1,3,4-oxadiazoles, and their structure-activity relationships are described. These compounds possessed excellent activity against Mycobacterium tuberculosis, including the clinically isolated multidrug (MDR) and extensively drug-resistant (XDR) strains, with no cross resistance with first or second-line anti-TB drugs. The minimum inhibitory concentration (MIC) values of the most promising compounds reached 0.03 μM. Furthermore, these compounds had a highly selective antimycobacterial effect because they were completely inactive against 4 gram positive and 4 gram negative bacteria and eight fungal strains and had low in vitro toxicity for four mammalian cell lines, including hepatic cell lines HepG2 and HuH7. Although the structure-activity relationship study showed that the presence of two nitro groups is highly beneficial for antimycobacterial activity, the analogues with a trifluoromethyl group instead of one of the nitro groups maintained a high antimycobacterial activity, which indicates the possibility for further structural optimization of this class of antitubercular agents.
Design and optimization of N-acylhydrazone pyrimidine derivatives as E. coli PDHc E1 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study
He, Haifeng,Xia, Hongying,Xia, Qin,Ren, Yanliang,He, Hongwu
, p. 5652 - 5661 (2017/10/09)
By targeting the thiamin diphosphate (ThDP) binding site of Escherichia coli (E. coli) pyruvate dehydrogenase multienzyme complex E1 (PDHc E1), a series of novel ‘open-chain’ classes of ThDP analogs A, B, and C with N-acylhydrazone moieties was designed and synthesized to explore their activities against E. coli PHDc E1 in vitro and their inhibitory activity against microbial diseases were further evaluated in vivo. As a result, A1–23 exhibited moderate to potent inhibitory activities against E. coli PDHc E1 (IC50 = 0.15–23.55 μM). The potent inhibitors A13, A14, A15, C2, had strong inhibitory activities with IC50 values of 0.60, 0.15, 0.39 and 0.34 μM against E. coli PDHc E1 and with good enzyme-selective inhibition between microorganisms and mammals. Especially, the most powerful inhibitor A14 could 99.37% control Xanthimonas oryzae pv. Oryzae. Furthermore, the binding features of compound A14 within E. coli PDHc E1 were investigated to provide useful insights for the further construction of new inhibitor by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that A14 had most powerful inhibition against E. coli PDHc E1 due to the establishment of stronger interaction with Glu571, Met194, Glu522, Leu264 and Phe602 at active site of E.coli PDHc E1. It could be used as a lead compound for further optimization, and may have potential as a new microbicide.
Synthesis, spectral analysis and antibacterial evaluation of 5-substituted-1,3,4-oxadiazol-2-yl 4-(4-methylpiperidin-1-ylsulfonyl)benzyl sulfides
Aziz-Ur-Rehman,Ahtzaz, Samreen,Abbasi, Muhammad Athar,Siddiqui, Sabahat Zahra,Rasool, Shahid,Ahmad, Irshad
, p. 3370 - 3375 (2017/05/22)
Owing to valuable biological activities of 1,3,4-oxadiazole, sulfamoyl and piperidine functionalities, some new 1-(4-{[(5-substituted-1,3,4-oxadiazol-2-yl) thio]methyl}benzene sulfonyl)-4-methylpiperidine (6a-o) derivatives have been introduced. The target molecules were synthesized from different aralkyl/aryl carboxylic acids, 1a-o, through a series of steps. First the compounds, 1a-o, were converted to heterocyclic 1,3,4-oxadiazole nucleophiles, 4a-o. Second an electrophile as 1-(4-bromomethylbenzenesulfonyl)-4-methylpiperidine (5) was synthesized from 4-methylpiperidine. Finally the target compounds, 6a-o, were prepared by reacting 4a-o with 5 in DMF and LiH. The final compounds were structurally elucidated by spectral data of IR, 1H-NMR and EI-MS. All the compounds were screened for their antibacterial evaluation and found to exhibit valuable results.
Synthesis and pharmacological screening: Sulfa derivatives of 2-pipecoline-bearing 1,3,4-oxadiazole core
Aziz-ur-Rehman,Arif,Abbasi,Siddiqui,Rasool,Shah
, p. 328 - 339 (2017/07/04)
An electrophile, 1-(4-(bromomethylbenzenesulfonyl)-2-methylpiperidine, was synthesized by the reaction of 2-methylpiperidine (2-pipecoline) and 4-bromomethylbenzenesulfonyl chloride in a weak basic medium under pH control. A series of nucleophiles, 5-aryl/aralkyl-1,3,4-oxadiazol-2-thiols, were synthesized from corresponding carboxylic acids in three steps. The title molecules were synthesized by coupling the electrophile to nucleophiles in an aprotic medium using LiH as an activator. The structures of all synthesized compounds were corroborated through IR, 1H NMR, and EI-MS techniques. All the compounds were screened for their pharmacological behavior, particularly, antibacterial and enzyme inhibitory activities. Notably efficient results were obtained against both gram-positive and gram-negative bacterial strains. Regarding enzyme inhibition, compounds were efficient against acetylcholinesterase and butyrylcholinesterase.
Rational design, synthesis and biological evaluation of 1,3,4-oxadiazole pyrimidine derivatives as novel pyruvate dehydrogenase complex E1 inhibitors
He, Haifeng,Wang, Wei,Zhou, Yuan,Xia, Qin,Ren, Yanliang,Feng, Jiangtao,Peng, Hao,He, Hongwu,Feng, Lingling
, p. 1879 - 1888 (2016/04/05)
On the basis of previous study on 2-methylpyrimidine-4-ylamine derivatives I, further synthetic optimization was done to find potent PDHc-E1 inhibitors with antibacterial activity. Three series of novel pyrimidine derivatives 6, 11 and 14 were designed and synthesized as potential Escherichia coli PDHc-E1 inhibitors by introducing 1,3,4-oxadiazole-thioether, 2,4-disubstituted-1,3-thiazole or 1,2,4-triazol-4-amine-thioether moiety into lead structure I, respectively. Most of 6, 11 and 14 exhibited good inhibitory activity against E. coli PHDc-E1 (IC50 0.97-19.21 μM) and obvious inhibitory activity against cyanobacteria (EC50 0.83-9.86 μM). Their inhibitory activities were much higher than that of lead structure I. 11 showed more potent inhibitory activity against both E. coli PDHc-E1 (IC50 50 50 = 0.97 μM) and cyanobacteria (EC50 = 0.83 μM). The possible interactions of the important residues of PDHc-E1 with title compounds were studied by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that 11d had more potent inhibitory activity than that of 14d or I due to its 1,3,4-oxadiazole moiety with more binding position and stronger interaction with Lsy392 and His106 at active site of E. coli PDHc-E1.
Synthesis, Characterization and Energetic Properties of 1,3,4-Oxadiazoles
Wang, Zuoquan,Zhang, Hong,Killian, Benjamin J.,Jabeen, Farukh,Pillai, Girinath G.,Berman, Heather M.,Mathelier, Michael,Sibble, Ashani J.,Yeung, Justin,Zhou, Wenfeng,Steel, Peter J.,Hall, C. Dennis,Katritzky, Alan R.
, p. 5183 - 5188 (2015/08/18)
An efficient cyclization between nitro-substituted benzoic acids and nitro-substituted benzohydrazides affords 1,3,4-oxadiazoles. Facile synthesis and a broad substrate scope produce a range of compounds, some of them with potential as high-energy compounds. Heats of formation (ΔHf) and densities (ρ) were calculated, and heats of decomposition (ΔHd) and combustion (ΔHc) were determined experimentally. The densities of seven of the synthesized compounds were determined by gas pycnometry, and the respective values of detonation velocity (VD), detonation pressure (PD) and specific impulse (ISP) were calculated using the EXPLO5 program. An X-ray structure of 2-(2,4-dinitrophenyl)-5-(3,5-dinitrophenyl)-1,3,4-oxadiazole (4n) revealed the non-planarity of the molecule and afforded a crystal density of 1.698 (at 120 K), close to the pycnometric value of 1.64 at room temperature. Efficient cyclization between nitro-substituted benzohydrazides and nitro-substituted benzoic acids affords energetic 1,3,4-oxadiazoles.
