- Molecular diversity in cyclization of Ugi-products leading to the synthesis of 2,5-diketopiperazines: computational study
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Abstract: Ugi-adducts were obtained via a one-pot four-component reaction of divergent aldehydes, amines, aroylacrylic acids and isocyanide in methanol. These products were subjected to intramolecular Michael addition in the presence of K2COsu
- Zadsirjan, Vahideh,Shiri, Morteza,Heravi, Majid M.,Hosseinnejad, Tayebeh,Shintre, Suhas A.,Koorbanally, Neil A.
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- Base-Promoted Annulative Difluoromethylenation of Enaminones with BrCF2CO2Et toward 2,2-Difluorinated 2,3-Dihydrofurans
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A practical method for the synthesis of 2,2-difluorinated 2,3-dihydrofurans has been established via the [4 + 1] annulation of enaminones and BrCF2CO2Et with Na2CO3 promotion. This new protocol does not employ any transition metal reagent and enables the annulative difluoromethylation by the partial cleavage of the C═C double bond. In addition, the further treatment with hydrochloric acid in one pot leads to β-keto enoic acids (4-oxo-2-butenoic acids) via a formal enaminone C-N carboxylation.
- Ying, Jinbiao,Liu, Ting,Liu, Yunyun,Wan, Jie-Ping
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p. 2404 - 2408
(2022/04/07)
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- Microwave-assisted synthesis of 4-oxo-2-butenoic acids by aldol-condensation of glyoxylic acid
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4-Oxobutenoic acids are useful as biologically active species and as versatile intermediates for further derivatisation. Currently, routes to their synthesis can be problematic and lack generality. Reaction conditions for the synthesis of 4-oxo-2-butenoic
- Gai, Conghao,Leach, Andrew G.,Liu, Hang,Sprenger, Lukas J.,Uguen, Mélanie,Waring, Michael J.
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p. 30229 - 30236
(2021/10/20)
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- Isocyanide-based MCRs: Diastereoselective cascade synthesis of perfluoroalkylated pyrano[3,4-c]pyrrole derivatives
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The highly diastereoselective synthesis of perfluoroalkyl-containing pyrano[3,4-c]pyrroles has been accomplished via a cascade process involving Michael addition, Passerini-type reaction, Mumm rearrangement and an oxo-Diels–Alder reaction. This domino tra
- Yang, Shanxue,Yao, Lan,Fan, Zhenhua,Han, Jing,Chen, Jie,He, Weimin,Deng, Hongmei,Shao, Min,Zhang, Hui,Cao, Weiguo
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supporting information
(2021/02/03)
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- Metal-free reduction of unsaturated carbonyls, quinones, and pyridinium salts with tetrahydroxydiboron/water
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A series of unsaturated carbonyls, quinones, and pyridinium salts have been effectively reduced to the corresponding saturated carbonyls, dihydroxybenzenes, and hydropyridines in moderate to high yields with tetrahydroxydiboron/water as a mild, convenient, and metal-free reduction system. Deuterium-labeling experiments have revealed this protocol to be an exclusive transfer hydrogenation process from water. This journal is
- Li, Tiejun,Peng, Henian,Tang, Wenjun,Tian, Duanshuai,Xu, Guangqing,Yang, He
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p. 4327 - 4337
(2021/05/31)
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- Design, synthesis, and bioevaluation of a novel class of (E)-4-oxo-crotonamide derivatives as potent antituberculosis agents
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A series of novel (E)-4-oxo-2-crotonamide derivatives were designed and synthesized to find potent antituberculosis agents. All the target compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv(MTB). Results reveal that 4-phenyl moiety at part A and short methyl group at part C were found to be favorable. Most of the derivatives displayed promising activity against MTB with MIC ranging from 0.125 to 4 μg/mL. Especially, compound IIIa16 was found to have the best activity with MIC of 0.125 μg/mL against MTB and with MIC in the range of 0.05–0.48 μg/mL against drug-resistant clinical MTB isolates.
- Ren, Jinfeng,Xu, Jian,Zhang, Guoning,Xu, Changliang,Zhao, LiLi,You, XueFu,Wang, Yucheng,Lu, Yu,Yu, Liyan,Wang, Juxian
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p. 539 - 543
(2019/01/09)
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- Design, synthesis and biological evaluation of benzoylacrylic acid shikonin ester derivatives as irreversible dual inhibitors of tubulin and EGFR
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In this study, a series of shikonin derivatives combined with benzoylacrylic had been designed and synthesized, which showed an inhibitory effect on both tubulin and the epidermal growth factor receptor (EGFR). In vitro EGFR and cell growth inhibition assay demonstrated that compound PMMB-317 exhibited the most potent anti-EGFR (IC50 = 22.7 nM) and anti-proliferation activity (IC50 = 4.37 μM) against A549 cell line, which was comparable to that of Afatinib (EGFR, IC50 = 15.4 nM; A549, IC50 = 6.32 μM). Our results on mechanism research suggested that, PMMB-317 could induce the apoptosis of A549 cells in a dose- and time-dependent manner, along with decrease in mitochondrial membrane potential (MMP), production of ROS and alterations in apoptosis-related protein levels. Also, PMMB-317 could arrest cell cycle at G2/M phase to induce cell apoptosis, and inhibit the EGFR activity through blocking the signal transduction downstream of the mitogen-activated protein MAPK pathway and the anti-apoptotic kinase AKT pathway; typically, such results were comparable to those of afatinib. In addition, PMMB-317 could suppress A549 cell migration through the Wnt/β-catenin signaling pathway in a dose-dependent manner. Additionally, molecular docking simulation revealed that, PMMB-317 could simultaneously combine with EGFR protein (5HG8) and tubulin (1SA0) through various forces. Moreover, 3D-QSAR study was also carried out, which could optimize our compound through the structure-activity relationship analysis. Furthermore, the in vitro and in vivo results had collectively confirmed that PMMB-317 might serve as a promising lead compound to further develop the potential therapeutic anticancer agents.
- Bao, Jia-Xin,Fu, Jiang-Yan,Han, Hong-Wei,Lin, Hong-Yan,Lu, Gui-Hua,Lu, Yun-Ting,Qi, Jin-Liang,Sun, Wen-Xue,Wang, Ming-Yue,Wang, Xiao-Ming,Wang, Yin-Song,Wen, Zhong-Ling,Yang, Min-Kai,Yang, Yong-Hua
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- A method for preparing [...] (by machine translation)
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The invention discloses a method for synthesizing [...], existing technology with the different is, first of all the toluene with maleic anhydride Friedel-crafts reaction to obtain the 4 - oxo - 4 - (4 - methyl phenyl) - 2 - butenoic, then the same halogen addition to obtain the 3 - halo - 4 - oxo - 4 - (4 - methyl phenyl) - butyric acid, the esterification reaction, the ring, to obtain 2 - (6 - methyl - 2 - P-imidazole [1, 2 - α] pyridine - 3 - yl) acetate, the hydrolysis, acidifying the resulting [...]. The method of the invention, obtaining the high-purity [...], the whole synthetic route less steps, high yield, low cost, less impurities, is suitable for industrial production. (by machine translation)
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Paragraph 0015; 0018; 0021
(2019/01/13)
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- Substituted 4-oxo-crotonic acid derivatives as a new class of protein kinase B (PknB) inhibitors: synthesis and SAR study
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Protein kinase B (PknB) is an essential serine/threonine protein kinase required for Mycobacterium tuberculosis (M. tb) cell division and cell-wall biosynthesis. A high throughput screen using PknB identified a (E)-4-oxo-crotonic acid inhibitor, named YH-8, which was used as a scaffold for SAR investigations. A significant improvement in enzyme affinity was achieved. The results indicated that the α,β-unsaturated ketone scaffold and “trans-” configuration are essential for the activity against PknB. And compounds with an aryl group, especially with electron-withdrawing substituents on benzene ring, exhibited four fold potency than that of YH-8.
- Xu, Changliang,Bai, Xiaoguang,Xu, Jian,Ren, Jinfeng,Xing, Yun,Li, Ziqiang,Wang, Juxian,Shi, Jingjing,Yu, Liyan,Wang, Yucheng
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p. 4763 - 4775
(2017/02/05)
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- Application of 4-oxo-2-crotonamide derivative to preparation of bacteriostatic agents
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The invention discloses application of a 4-oxo-2-crotonamide derivative to preparation of bacteriostatic agents. The structure of the 4-oxo-2-crotonamide derivative is shown as a formula (I). The 4-oxo-2-crotonamide derivative has a bacteriostatic effect; good antibacterial activity can be realized on methicillin-resistant staphylococcus aureus, methicillin-resistant staphylococcus epidermidis, vancomycin drug-resistant enterococcus faecalis, vancomycin drug-resistant enterococcus faecium, methicillin-sensitive staphylococcus aureus, methicillin-sensitive staphylococcus epidermidis, vancomycin-sensitive enterococcus faecalis and vancomycin-sensitive enterococcus faecium. The formula I is shown in the description.
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Paragraph 0072; 0073; 0074; 0103; 0104
(2017/07/22)
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- Synthesis of 1,5-benzodiazepine derivatives using p-toluenesulfonic acid as catalyst
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A series of substituted ethyl 4-oxo-4-phenylbut-2-enoates were prepared and reacted with substituted o-phenylenediamine, undergone Michael addition reactions and cyclodehydration to provide novel 4-phenyl-2,3-dihydro-1,5-benzodiazepine-2-carboxylate derivatives with excellent yields. The synthetic protocol fulfilled many green-chemical requirements by using simple catalyst p-toluenesulfonic acid as activator and ethanol as solvent at room temperature.
- Wang, Shasha,Hu, Lijuan,Cheng, Suyan,Wang, Lanzhi
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p. 419 - 424
(2015/01/30)
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- Hydrogen-bond-directed formal [5 + 1] annulations of oxindoles with ester-linked bisenones: Facile access to chiral spirooxindole δ-lactones
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A novel bifunctional thiourea catalyzed formal [5 + 1] cycloaddition of oxindoles and ester-linked bisenones was successfully developed. This strategy involves two sequential Michael additions, leading to spirooxindole δ-lactones with three contiguous ste
- Zhao, Shuai,Lin, Jun-Bing,Zhao, Yuan-Yuan,Liang, Yong-Min,Xu, Peng-Fei
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supporting information
p. 1802 - 1805
(2014/04/17)
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- Structure-activity relationship, cytotoxicity and mode of action of 2-ester-substituted 1,5-benzothiazepines as potent antifungal agents
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Our studies examined the structural features responsible for the antifungal activity of 2-ethoxycarbonyl-1,5-benzothiazepine (7a). Three series of 1,5-benzothiazepine derivatives were synthesized and screened for their antifungal activity. The results suggested that the ethoxycarbonyl group at the 2 position and the imine moiety on the seven-membered ring are essential for activity. The most potent of the synthesized analogues (7a, 7b) were further studied by evaluating their cytotoxicity and mode of action (for 7a). The results showed that compounds 7a and 7b were relatively safe for BV2 cells, but compound 7a interfered with Cryptococcus neoformans cell wall integrity by increasing the chitinase activity. Therefore, compound 7a was considered safe as an antifungal agent for animal cells. Three series of 1,5-benzothiazepine derivatives were synthesized and their antifungal activities were evaluated to determine the structure-activity relationships with respect to the antifungal activity of 2-ester-substituted 1,5-benzothiazepines. The effective antifungal compounds 7a and 7b were further studied for their antifungal activity, cytotoxicity and mechanism of action (for compound 7a). The results provided important information about this class of benzothiazepines. Copyright
- Kang, Wang,Du, Xingqiong,Wang, Lanzhi,Hu, Lijuan,Dong, Yuhuan,Bian, Yanqing,Li, Yuan
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p. 1305 - 1314
(2013/11/06)
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- Synthesis and evaluation of anticancer activity of some novel 6-aryl-2-(p-sulfamylphenyl)-pyridazin-3(2H)-ones
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A series of novel pyridazinone derivatives bearing benzenesulfonamide moiety (2a-h) has been synthesized by the condensation of appropriate aroylacrylic acid and 4-hydrazinobenzenesulfonamide hydrochloride in ethanol. Five derivatives (2a, 2b, 2d, 2g and 2h) were evaluated for their anticancer activity toward human cancer cell lines by the National Cancer Institute. The 2h showed remarkable activity against SR (leukemia) and NCI-H522 (non-small cell lung) with a GI50 value of less than 0.1 μM. It also displayed good activity against leukemia (CCRF-CEM, HL-60 (TB), K-562, MOLT-4, RPMI-8226), non-small cell lung cancer (NCI-H460), colon (HCT-116, HCT-15, HT29, KMI2, SW-620), CNS (SF-295), melanoma (MALME-3M, M14, MDA-MB-435 SK-MEL-5), ovarian (OVCAR-3, NCI/ADR-RES) and breast (MCF7) cancer cell lines with a GI 50 less than 1.0 μM. The acute toxicity study of 2h indicated that it is well tolerated intra-peritoneally (400 mg/kg) by athymic nude mice. The 2h may possibly be used as lead compound for developing new anticancer agents.
- Rathish,Javed, Kalim,Ahmad, Shamim,Bano, Sameena,Alam,Akhter, Mymoona,Pillai,Ovais, Syed,Samim, Mohammed
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scheme or table
p. 304 - 309
(2012/04/10)
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- Antiproliferative activity of aroylacrylic acids. Structure-activity study based on molecular interaction fields
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Antiproliferative activity of 27 phenyl-substituted 4-aryl-4-oxo-2-butenoic acids (aroylacrylic acids) toward Human cervix carcinoma (HeLa), Human chronic myelogenous leukemia (K562) and Human colon tumor (LS174) cell lines in vitro are reported. Compounds are active toward all examined cell lines. The most active compounds bear two or three branched alkyl or cycloalkyl substituents on phenyl moiety having potencies in low micromolar ranges. One of most potent derivatives arrests the cell cycle at S phase in HeLa cells. The 3D QSAR study, using molecular interaction fields (MIF) and derived alignment independent descriptors (GRIND-2), rationalize the structural characteristics correlated with potency of compounds. Covalent chemistry, most possibly involved in the mode of action of reported compounds, was quantitatively accounted using frontier molecular orbitals. Pharmacophoric pattern of most potent compounds are used as a template for virtual screening, to find similar ones in database of compounds screened against DTP-NCI 60 tumor cell lines. Potency of obtained hits is well predicted.
- Drakuli?, Branko J.,Stanojkovi?, Tatjana P.,?i?ak, ?eljko S.,Dabovi?, Milan M.
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supporting information; experimental part
p. 3265 - 3273
(2011/07/31)
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- Catalytic conjugate addition of indoles to 4-aryl-4-oxobut-2-enoates by FeCl3
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The conjugate addition of indoles to 4-aryl-4-oxobut-2-enoates was achieved with FeCl3 as a catalyst under mild conditions. The reaction was highly regioselective and afforded a variety of new 3-substituted indoles in good to excellent yields. Copyright
- Wang, Xiaoxia,Zhang, Yaohong,Xiao, Xiaohui,Li, Xinsheng
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supporting information; experimental part
p. 1284 - 1285
(2009/12/03)
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- 2-[(Carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids selectively suppressed proliferation of neoplastic human HeLa cells. A SAR/QSAR study
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A series of twenty alkyl-, halo-, and methoxy-aryl-substituted 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids were synthesized. The new compounds, called CSAB, suppressed proliferation of human cervix carcinoma, HeLa cells, in vitro in a concentration range of 0.644 to 29.48 μM/L. Two compounds exhibit antiproliferative activity in sub-micromolar concentrations (16, 19). Five compounds act in low micromolar concentrations ( 10). A strong structure-activity relationship, using estimated log P values and BCUT descriptors, was observed.
- Drakuli?, Branko J.,Jurani?, Zorica D.,Stanojkovi?, Tatjana P.,Jurani?, Ivan O.
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p. 5600 - 5603
(2007/10/03)
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- Gastric anti-secretory, anti-ulcer and cytoprotective properties of substituted (E)-4-phenyl- and heteroaryl-4-oxo-2-butenoic acids
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A class of anti-secretory, anti-ulcer and cytoprotective agents, the substituted (E)-4-phenyl and heteroaryl-4-oxo-2-butenoic acids, is described.This chemical structure is not related to those of any known anti-cholinergic drugs, histamine H2-receptor antagonists or prostaglandins.Five compounds, 4-(2-methoxyphenyl)- 15, 4-(4-methoxyphenyl)- 22, 4-(3,4-dimethoxyphenyl)- 32, 4-(3,4,5-trimethoxyphenyl)- 40, and 4-(2-furanyl)-4-oxo-2-butenoic acid 44, have cytoprotective activity at a very low dose (0.6 mg/kg, p.o.) and anti-secretory and anti-ulcer activities at higher doses.One of these compounds, RU 38086 40, has been selected for clinical evaluation.Keywords - anti-ulcer agents / cytoprotective agents / (E)-4-phenyl- and heteroaryl-4-oxo-2-butenoic acids.
- Bianchi, Mario,Butti, Alina,Christidis, Yani,Perronnet, Jacques,Barzaghi, Fernando,et al.
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- Syntheses of 1,5-Benzothiazepines: Part II - Synthesis of 4-Aryl-2-carboxy-2,3-dihydro-1,5-benzothiazepines
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β-Aroylacrylic acids (II) react with 2-aminothiophenols (I) in ethanol containing gl.acetic acid to give 4-aryl-2-carboxy-2,3-dihydro-1,5-benzothiazepines (VII).Their structures have been established by elemental analyses and spectral data (IR, PMR, 13C NMR and mass).
- Pant, Umesh C.,Gaur, B. S.,Chugh, Manju
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p. 947 - 950
(2007/10/02)
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