- An eco-friendly synthesis of 4-aryl-substituted pyrano-fuzed coumarins as potential pharmacological active heterocycles using molybdenum oxide nanoparticles as an effective and recyclable catalyst
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A green cascade three-component reaction between 4-hydroxycoumarin, malononitrile and a wide range of arylaldehydes by employing molybdenum oxide nanoparticles (MoO3 NPs) is described. By this achievement, some medicinally important products have been successfully synthesized in a one-pot under green conditions. Obtaining good to excellent yields of products, environmentally benign procedure, being easily handled, availability of starting materials, use of non-toxic solvents, and high recyclability of nano-catalysts are the most important advantages of this methodology.
- Pourshojaei, Yaghoub,Jadidi, Mohammad-Hossein,Eskandari, Khalil,Foroumadi, Alireza,Asadipour, Ali
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Read Online
- Synthesis and molecular modeling of new 2-benzylidenethiobarbituric acid derivatives as potent tyrosinase inhibitors agents
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New 2-benzylidenethiobarbituric acid-(benzyloxyphenyl) derivatives were designed, synthesized, and evaluated as tyrosinase inhibitors. The products can be divided into two groups: 4-hydroxybenzaldehyde derivatives and vanillin derivatives. Some of the 4-hydroxybenzaldehyde derivatives showed significant inhibitory activity while all vanillin derivatives have no inhibitory activities. It seems that the presence of the methoxy group on the internal aromatic ring prevents the ligand–enzyme interaction. According to the tyrosinase inhibitory assay, 5-(4-([4-Methylbenzyl]oxy)benzylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (4g) is the most potent antityrosinase agents with an IC50 value of 23.90 ± 0.08 μM. It showed even better inhibitory activity than kojic acid. The results of kinetic and molecular docking studies demonstrated that compound 4g acts as a noncompetitive inhibitor and can bind to some amino acids such as His263 and Val283 of the active site through Pi–alkyl and Pi–Pi interactions and areas around the active site via the hydrogen bond. In-silico adsorption, distribution, metabolism, excretion, and toxicity (ADMET) studies predicted that these products have good drug-likeness. All findings indicate the 2-benzylidenethiobarbituric acids with the benzyloxyphenyl tail have good potential for the treatment of melanogenesis compared to kojic acid.
- Chehardoli, Gholamabbas,Hajimahmoodi, Mannan,Kamari-aliabadi, Adel,Najafi, Zahra,Sabourian, Reyhaneh
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- Evolution of a 4-Benzyloxy-benzylamino Chemotype to Provide Efficacious, Potent, and Isoform Selective PPARα Agonists as Leads for Retinal Disorders
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Peroxisome proliferator-activated receptor alpha (PPARα) is expressed in retinal Müller cells, endothelial cells, and in retinal pigment epithelium; agonism of PPARα with genetic or pharmacological tools ameliorates inflammation, vascular leakage, neurodegeneration, and neovascularization associated with retinal diseases in animal models. As such, PPARα is a promising drug target for diabetic retinopathy and age-related macular degeneration. Herein, we report proof-of-concept in vivo efficacy in an streptozotocin-induced vascular leakage model (rat) and preliminary pharmacokinetic assessment of a first-generation lead 4a (A91). Additionally, we present the design, synthesis, and evaluation of second-generation analogues, which led to the discovery of 4u and related compounds that reach cellular potencies 2,700-fold selectivity for PPARα over other PPAR isoforms. These studies identify a pipeline of candidates positioned for detailed PK/PD and pre-clinical evaluation.
- Dou, Xiaozheng,Nath, Dinesh,Shin, Henry,Nurmemmedov, Elmar,Bourne, Philip C.,Ma, Jian-Xing,Duerfeldt, Adam S.
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p. 2854 - 2876
(2020/04/10)
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- Synthesis and biological evaluation of tryptophan-derived rhodanine derivatives as PTP1B inhibitors and anti-bacterial agents
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Several series of novel tryptophan-derived rhodanine derivatives were synthesized and identified as potential competitive PTP1B inhibitors and antibacterial agents. Among the compounds studied, 10b was found to have the best in vitro inhibition activity against PTP1B (IC50 = 0.36 ± 0.02 μM). In addition, the compounds also showed potent inhibition against other PTPs, especially CDC25B. Molecular docking analysis demonstrated that compounds 7c and 10b could occupy both the catalytic site and the adjacent pTyr binding site simultaneously. The compounds also showed higher levels of activity against gram-positive strains, the gram-negative strain Escherichia coli 1924, and multidrug-resistant gram-positive bacterial strains. Compounds 7c, 8c, 9e, 10a, and 10c had comparable or more potent antibacterial activity than the positive controls.
- Liu, Hongyan,Sun, Danwen,Du, Hang,Zheng, Changji,Li, Jingya,Piao, Huri,Li, Jia,Sun, Liangpeng
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p. 163 - 173
(2019/04/13)
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- Ultrasound-assisted and efficient knoevenagel condensation reaction catalyzed by silica sodium carbonate nanoparticles
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An efficient and ultrasound-assisted route to the synthesis of arylidene malononitriles/methylciano- or ethylciano acetates in a one-pot reaction catalyzed by silica sodium carbonate nanoparticles (SSC NPs) is described. In this reaction, SSC NPs demonstrated high efficiency as catalyst to obtain target products. By this achievement, a wide range of α,β-unsaturated compounds as Knoevenagel condensation products with good to excellent yields are obtained from reaction between numerous arylaldehydes, and malononitrile, methyl cianoacetate or ethyl cianoacetate. Target products which prepared in high yield and high purity can be candidate as important biologically active molecules. This method is an easy, cheap, rapid and highly efficient for the synthesis of desired products. In addition, capability of catalyst to separate from reaction mixture and reuse in further runs and being compatible with green chemistry are considered as other advantages of this procedure. All products were deduced from their FT-IR and FT-NMR spectroscopic and elemental analysis data.
- Pourshojaei, Yaghoub,Nikzad, Maryam,Eskandari, Khalil,Darijani, Mohammad-Hossein,Hassanzadeh, Abdolreza,Faghih-Mirzaei, Ehsan,Asadipour, Ali
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- Nitrogen-containing heterocyclic amide derivative and use thereof
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The present invention discloses a nitrogen-containing heterocyclic amide derivative and use thereof, and in particular, the present invention relates to a novel class of nitrogen-containing heterocyclic amide derivatives and pharmaceutical compositions co
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Paragraph 0256-0257; 0353; 0355-0356
(2019/01/06)
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- Sophoridine pyrrole, indole derivative and preparation method and application thereof
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The invention relates to a sophoridine pyrrole, indole derivative. The invention discloses a chemical structure of the compound and further discloses a preparation method of the compound. In vitro anti-tumor activity researches show that anti-tumor drugs
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Paragraph 0191; 0193; 0195; 0206
(2018/09/08)
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- Synthesis and biological evaluation of dihydrotriazine derivatives as potential antibacterial agents
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A series of 1,4-dihydro-1,3,5-triazine derivatives were designed and synthesized and their antibacterial and antifungal activities were evaluated. Most of the synthesized compounds showed potent inhibition of several Gram-positive bacterial strains (including multidrug-resistant clinical isolates) and Gram-negative bacterial strains, with minimum inhibitory concentrations (MICs) in the range of 2.1–181.2?μmol/L. Compounds 7a and 7c presented the most potent inhibitory activities against Gram-positive bacteria (e.g., Staphylococcus aureus 4220), Gram-negative bacteria (e.g., Escherichia coli 1924), and the fungus Candida albicans 7535, with MICs of 2.1 or 4.1?μmol/L. Especially, compound 7a was the most potent, with an MIC of 2.1?μmol/L against four multidrug-resistant, Gram-positive bacterial strains. The cytotoxic activity of the compound 7a, 7c and 7f was assessed in HepG2 cells, and the results suggest that 1,4-dihydro-1,3,5-triazine derivatives bearing a 6-benzyloxynaphthalen moiety are interesting scaffolds for the development of novel antibacterial agents.
- Zhang, Tian-Yi,Li, Chao,Tian, Yu-Shun,Li, Jia-Jun,Sun, Liang-Peng,Zheng, Chang-Ji,Piao, Hu-Ri
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supporting information
p. 1737 - 1742
(2017/07/27)
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- Design, synthesis, and biological evaluation of novel thiazolidinediones as PPAR3/FFAR1 dual agonists
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Diabetes mellitus is a chronic metabolic disorder that affects more than 180 million people worldwide. Peroxisome proliferator activated receptors (PPARs) are a group of nuclear receptors that have been targeted by the thiazolidinedione (TZD) class of compounds for the management of type II diabetes. PPAR3 is known to regulate adipogenesis and glucose metabolism. Another emerging target for the design of antidiabetic agents is the free fatty acid receptor 1 (FFAR1), previously known as GPR40. Agonists of this receptor were found to enhance insulin secretion in diabetic patients. It has been reported that some thiazolidinediones (TZDs) activate FFAR1 with micromolar potency. In this study, based on docking studies into the crystal structure of PPAR3 and a homology model of FFAR1, nineteen compounds were designed, synthesized, and biologically tested for agonistic activity on both receptors. Nine compounds showed promising dual activity, with two compounds, 11a and 5b, having affinities in the low micromolar range on both targets. These molecules represent the first antidiabetic agents that could act as insulin sensitizers as well as insulin secretagogues.
- Darwish, Khaled M.,Salama, Ismail,Mostafa, Samia,Gomaa, Mohamed S.,Helal, Mohamed A.
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p. 157 - 172
(2016/01/16)
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- Synthesis and analysis of anticonvulsant activities of new 4-[2-(4-alkoxybenzylamino)ethyl]-2H-1,2,4-triazol-3(4H)-one derivatives
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The present study involved the design and synthesis of new substituted 4-[2-(4-alkoxybenzylamino) ethyl]-2H-1,2,4-triazol-3(4H)-one derivatives (8a-w) starting from 1,2-ethanediamine. The final compounds were screened for their in vivo anticonvulsant activities and neurotoxicities by maximal electroshock (MES) and rotarod tests, respectively. Among the compounds studied, 4-[2-(4-butoxybenzylamino)ethyl]-2H-1,2,4-triazol-3(4H)-one hydrochloride (8b) was found by intraperitoneal administration in mice to be the most potent compound with a median effective dose (ED50) value of 33.2 mg/kg and a high protective index (PI) value of 11.4. Compound 8b showed significant oral activity against MES-induced seizures in mice with an ED50 value of 83.1 mg/kg and a PI of 18.1. The results demonstrated that compound 8b possessed better anticonvulsant activity and higher safety than the marketed drug carbamazepine.
- Shen, Qing-Kun,Wang, Shi-Ben,Gong, Guo-Hua,Yin, Xiu-Mei,Quan, Zhe-Shan
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p. 430 - 438
(2015/06/22)
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- Selected michael additions to thiophene-containing analogues of chalcone
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Using thiophene-containing analogues of chalcone as substrates, a series of Michael additions were investigated. Thia-Michael addition of 4-chlorothiophenol led to 1-(substituted aryl)-3-(4-chlorophenylmercapto)-1-(2-thienyl)-1-propanones, whereas catalyt
- Roman, Gheorghe
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p. 751 - 760
(2015/11/24)
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- Synthesis and antimicrobial evaluation of L-phenylalanine-derived C5-substituted rhodanine and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone
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Four novel series of compounds, including the l-phenylalanine-derived C5-substituted rhodanine (6a-q, 7a-j) and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone (9a-e, 11a-e) have been designed, synthesized, characterized, and evaluated for their antibacterial activity. Some of these compounds showed significant antibacterial activity against Gram-positive bacterias, especially against the strains of multidrug-resistant clinical isolates, among which compounds 6c-e, 6g, 6i, 6j and 6q exhibiting high levels of antimicrobial activity against Staphylococcus aureus RN4220 with minimum inhibitory concentration (MIC) values of 2 μg/mL. Compound 6q showed the most potent activity of all of the compounds against all of the test multidrug-resistant clinical isolates tested. Unfortunately, however, none of the compounds were active against Gram-negative bacteria at 64 μg/mL.
- Zheng, Chang-Ji,Song, Ming-Xia,Wu, Yan,Sun, Liang-Peng,Li, Yin-Jing,Piao, Hu-Ri,Jin, Xin,Yu, Li-Jun
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p. 203 - 209,7
(2012/12/12)
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- Structure-based design of novel boronic acid-based inhibitors of autotaxin
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Autotaxin (ATX) is a secreted phosphodiesterase that hydrolyzes the abundant phospholipid lysophosphatidylcholine (LPC) to produce lysophosphatidic acid (LPA). The ATX-LPA signaling axis has been implicated in inflammation, fibrosis, and tumor progression
- Albers, Harald M. H. G.,Hendrickx, Loes J. D.,Van Tol, Rob J. P.,Hausmann, Jens,Perrakis, Anastassis,Ovaa, Huib
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supporting information; experimental part
p. 4619 - 4626
(2011/09/14)
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