- Environmentally benign and energy efficient methodology for condensation: An interesting facet to the classical Perkin reaction
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We have reported use of biodegradable deep eutectic solvent (DES) based on choline chloride and urea, for the synthesis of cinnamic acid and its derivatives via Perkin reaction. The reaction proceeds efficiently under mild condition without use of additional catalyst with better yields. Ease of recovery and reusability of solvent with consistent activity makes this method efficient and environmentally benign. This method is also energy efficient and easy to handle.
- Pawar, Poonam Mahadev,Jarag, Krishna Jagannath,Shankarling, Ganapati Subray
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Read Online
- Coordination polymers of organic polymers synthesized via photopolymerization of single crystals: Two-dimensional hydrogen bonding layers with amazing shock absorbing nature
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Crystalline coordination polymers of organic polymers (CPOPs) were synthesized via photopolymerization of Ag(i) coordination polymers of dienes which have a self-templating nature due to the formation of N-H...O hydrogen bonded layers. The shock absorbing nature of the H-bonded layer facilitated the SCSC [2+2] transformation upon irradiation to produce CPOPs. This journal is the Partner Organisations 2014.
- Garai, Mousumi,Biradha, Kumar
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- Synthesis of cinnamic acid derivatives in a water-insoluble ionic liquid
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A number of cinnamic acid derivatives have been synthesised from commercially available aromatic aldehydes and propanedioic acid in a water-insoluble ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate, [bmim]PF6) in high yields in the presence of small catalytic amounts of piperidine. The ionic liquid can be reused at least five times.
- Zhang, Wensheng,Xu, Wenjing,Liu, Mei,Yan, Yuerong,Sun, Yuezhi,Zhang, Sheli
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- Isoreticular Expansion of Metal–Organic Frameworks via Pillaring of Metal Templated Tunable Building Layers: Hydrogen Storage and Selective CO2 Capture
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The deliberate construction of isoreticular eea-metal–organic frameworks (MOFs) (Cu-eea-1, Cu-eea-2 and Cu-eea-3) and rtl-MOFs (Co-rtl-1 and Co-rtl-2) has been accomplished based on the ligand-to-axial pillaring of supermolecular building layers. The use of different metal ions resulted in two types of supermolecular building layers (SBLs): Kagome (kgm) and square lattices (sql) which further interconnect to form anticipated 3D-MOFs. The isoreticular expansion of (3,6)-connected Cu-MOFs has been achieved with desired eea-topology based on kgm building layers. In addition, two (3,6)-connected Co-rtl-MOFs were also successfully constructed based on sql building layers. The Cu-eea-MOFs were shown to act as hydrogen storage materials with appreciable amount of hydrogen uptake abilities. Moreover Cu-eea-MOFs have also exhibited remarkable CO2 capture ability at ambient condition compared to nitrogen and methane, due to the presence of amide functionalities.
- Maity, Kartik,Nath, Karabi,Sinnwell, Michael A.,Motkuri, Radha Kishan,Thallapally, Praveen K.,Biradha, Kumar
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- Structural features of pyridylcinnamic acid dimers and their extended hydrogen-bonded aggregations
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The conformational as well as the structure-forming properties of E-3-(x-pyridyl)propenoic acids (x = 2, 3 or 4) have been studied with a combination of computational and spectroscopic methods. IR spectroscopy revealed that in the solid state the zwitterionic species predominate, while NMR measurements showed that dimers, kept together by strong CO?HO hydrogen bonds, were formed in a dipolar aprotic solvent (DMSO). In concentrated solution, extended aggregation occurred through the cooperative effect of (aromatic) C-H?N weak hydrogen bonds. Conformational search was performed at the HF/6-31G(d,p) level of theory. Comparison with experimental values as well as benchmarking calculations at several different levels of theory to probe the performance of the methods, B3LYP/6-31G++(d,p) method was found to be able to provide reasonable geometries as well as quantitative formation energies for the dimers and the tetramers, too.
- Csankó,Ruusuvuori,Tolnai,Sipos,Berkesi,Pálinkó
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- Strategic Approach to 8-Azacoumarins
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8-Azacoumarins have emerged as a promising class of compounds but are rarely explored due to challenging access. A novel, general, and practical method is provided for this class of compounds. The key lactonization step employs trans-acrylic acid attached pyridine N-oxides as the starting material, with acetic anhydride as both the activation agent and the solvent. Multiple transformations were involved in this reaction, including conjugate addition, nucleophilic aromatic substitution, and elimination. These studies provide the basis for access to 8-azacoumarins, enabling future work including the discovery and development of novel coumarin-type drugs, fluorescent probes, photolabile protecting groups, and other active molecules.
- Wang, Dong,Wang, Yuxi,Zhao, Junjie,Shen, Meng,Hu, Jianyong,Liu, Zhenlin,Li, Linna,Xue, Furen,Yu, Peng
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Read Online
- Dual Nickel/Ruthenium Strategy for Photoinduced Decarboxylative Cross-Coupling of α,β-Unsaturated Carboxylic Acids with Cycloketone Oxime Esters
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Herein, a dual nickel/ruthenium strategy is developed for photoinduced decarboxylative cross-coupling between α,β-unsaturated carboxylic acids and cycloketone oxime esters. The reaction mechanism is distinct from previous photoinduced decarboxylation of α,β-unsaturated carboxylic acids. This reaction might proceed through a nickelacyclopropane intermediate. The C(sp2)-C(sp3) bond constructed by the aforementioned reaction provides an efficient approach to obtaining various cyanoalkyl alkenes, which are synthetically valuable organic skeletons in organic and medicinal chemistry, under mild reaction conditions. The protocol tolerates many critical functional groups and provides a route for the modification of complex organic molecules.
- Gao, Ang,Jiang, Run-Chuang,Liu, Chuang-Chuang,Liu, Qi-Le,Lu, Xiao-Yu,Xia, Ze-Jie
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supporting information
p. 8829 - 8842
(2021/06/30)
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- Iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabled aldehyde C-H methylation
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A practical and general iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabling aldehyde C-H methylation for the synthesis of methyl ketones has been developed. This mild, operationally simple method uses ambient air as the sole oxidant and tolerates sensitive functional groups for the late-stage functionalization of complex natural-product-derived and polyfunctionalized molecules.
- Gong, Pei-Xue,Xu, Fangning,Cheng, Lu,Gong, Xu,Zhang, Jie,Gu, Wei-Jin,Han, Wei
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supporting information
p. 5905 - 5908
(2021/06/18)
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- Photocatalytic decarboxylative alkenylation of α-amino and α-hydroxy acid-derived redox active esters by NaI/PPh3 catalysis
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Herein, we report the photocatalytic decarboxylative alkenylation reactions of N-(acyloxy)phthalimide derived from α-amino and α-hydroxy acids with 1,1-diarylethene, and with cinnamic acid derivatives through double decarboxylation, using sodium iodide and triphenylphosphine as redox catalysts. The reaction proceeds under mild irradiation conditions with visible blue light (440 nm or 456 nm) in an acetone solvent without recourse to transition-metal or organic dye based photoredox catalysts. The reaction proceeds via photoactivation of a transiently self-assembled chromophore from N-(acyloxy)phthalimide and NaI/PPh3. Solvation plays a crucial role in the reactivity.
- Fu, Ming-Chen,Fu, Yao,Shang, Rui,Wang, Ya-Ting,Zhao, Bin
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supporting information
p. 2495 - 2498
(2020/03/06)
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- Orthoquinone compound, as well as preparation method and medicinal application thereof
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The invention discloses an active small molecular compound simultaneously targeted to NQO1 and NAMPT, as well as a preparation method and a medicinal application thereof, and particularly relates to an orthoquinone compound or a pharmaceutically acceptable salt, solvate, predrug, ester, raceme and isomer thereof, and a medicine composition comprising the compounds, and applications of these compounds and medicine compositions in preparation of anti-tumor drugs. In the invention, by reasonably jointing an activating substrate tanshinone IIA of the NQO1 and the pharmacophores on the NAMPT inhibitor, the NQO1 substrate/NAMPT inhibitor is obtained, so that the compounds can be reductively activated by the NQO1 and meanwhile can inhibit the activity of the NAMPT, thus consuming the NAD+ and inhibiting biosynthesis of the NAD+ and showing a better tumor inhibiting activity. The orthoquinone compounds or medicine compositions thereof that simultaneously target to the NQO1 and the NAMPT have extensive application prospect and are hopeful to be anti-tumor drugs.
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Paragraph 0263-0264; 0267-0268
(2020/04/17)
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- Synthesis and biological evaluation of 2,2-dimethylbenzopyran derivatives as potent neuroprotection agents
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The development of novel neuroprotection agents is of great significance for the treatment of ischemic stroke. In this study, a series of compounds comprising 2,2-dimethylbenzopyran groups and cinnamic acid groups have been synthesized. Preferential combination principles and bioisostere that improved the neuroprotective effect of the compounds were identified for this series via biological activity assay in vitro. Meanwhile, a functional reversal group of the acrylamide amide resulted in the most active compounds. Among them, BN-07 significantly improved the morphology of neurons and obviously increased cell survival rate of primary neurons induced by oxygen glucose deprivation (OGD), superior to clinically used anti-ischemic stroke drug edaravone (Eda). Overall, our findings may provide an alternative strategy for the design of novel anti-ischemic stroke agents with more potency than Eda.
- Du, Fangyu,Zhou, Qifan,Fu, Xiaoxiao,Shi, Yajie,Chen, Yuanguang,Fang, Wuhong,Yang, Jingyu,Chen, Guoliang
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p. 2498 - 2508
(2019/02/01)
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- Small molecule inhibitor, preparation method thereof and application of small molecule inhibitor in treatment of multiple myeloma
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The invention discloses a small molecule inhibitor, a preparation method thereof and application of the small molecule inhibitor in treatment of multiple myeloma. The small molecule inhibitor has a structural formula shown in a formula I or formula II or formula III or formula IV. The invention also provides the preparation method of the small molecule inhibitor. The small molecule inhibitor can be used for inhibiting the activity of Bruton tyrosine protein kinase, and therefore can be applied to the treatment of the multiple myeloma, such as IgE-type multiple myeloma.
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Paragraph 0142-0145
(2018/05/16)
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- Semi-synthesis and Structure–Activity Relationship of Neuritogenic Oleanene Derivatives
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(3S,4R)-23,28-Dihydroxyolean-12-en-3-yl (2E)-3-(3,4-dihydroxyphenyl)acrylate (1 a), which possesses significant neuritogenic activity, was isolated from the traditional Chinese medicine (TCM) plant, Desmodium sambuense. To confirm the structure and to assess biological activity, we semi-synthesized 1 a from commercially available oleanolic acid. A series of novel 1 a derivatives was then designed and synthesized for a structure–activity relationship (SAR) study. All synthetic derivatives were characterized by analysis of spectral data, and their neuritogenic activities were evaluated in assays with PC12 cells. The SAR results indicate that the number and position of the hydroxy groups on the phenyl ring and the triterpene moiety, as well as the length of the (saturated or unsaturated) alkyl chain that links the phenyl ring with the triterpene critically influence neuritogenic activity. Among all the tested compounds, 1 e [(3S,4R)-23,28-dihydroxyolean-12-en-3-yl (2E)-3-(3,4,5-trihydroxyphenyl)acrylate] was found to be the most potent, inducing significant neurite outgrowth at 1 μm.
- Bian, Linglin,Cao, Shining,Cheng, Lihong,Nakazaki, Atsuo,Nishikawa, Toshio,Qi, Jianhua
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supporting information
p. 1972 - 1977
(2018/09/06)
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- Discovery of caffeic acid phenethyl ester derivatives as novel myeloid differentiation protein 2 inhibitors for treatment of acute lung injury
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Myeloid differentiation protein 2 (MD2) is an essential molecule which recognizes lipopolysaccharide (LPS), leading to initiation of inflammation through the activation of Toll-like receptor 4 (TLR4) signaling. Caffeic acid phenethyl ester (CAPE) from propolis of honeybee hives could interfere interactions between LPS and the TLR4/MD2 complex, and thereby has promising anti-inflammatory properties. In this study, we designed and synthesized 48 CAPE derivatives and evaluated their anti-inflammatory activities in mouse primary peritoneal macrophages (MPMs) activated by LPS. The most active compound, 10s, was found to bind with MD2 with high affinity, which prevented formation of the LPS/MD2/TLR4 complex. The binding mode of 10s revealed that the major interactions with MD2 were established via two key hydrogen bonds and hydrophobic interactions. Furthermore, 10s showed remarkable protective effects against LPS-caused ALI (acute lung injury) in vivo. Taken together, this work provides new lead structures and candidates as MD2 inhibitors for the development of anti-inflammatory drugs.
- Chen, Lingfeng,Jin, Yiyi,Chen, Hongjin,Sun, Chuchu,Fu, Weitao,Zheng, Lulu,Lu, Min,Chen, Pengqin,Chen, Gaozhi,Zhang, Yali,Liu, Zhiguo,Wang, Yi,Song, Zengqiang,Liang, Guang
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p. 361 - 375
(2017/12/07)
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- Novel NAMPT and IDO dual inhibitor, and preparation method and medical applications thereof
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The invention discloses a novel NAMPT and IDO dual inhibitor, and a preparation method and medical applications thereof, and more specifically relates to a furazan compound, or pharmaceutically acceptable salts, solvates, prodrugs, esters, racemic compounds, and isomers of the furazan compound, and pharmaceutical compositions containing the furazan compound, and applications of the furazan compound or the pharmaceutical compositions in the field of anti-tumor drug preparation. According to the preparation method, reasonable combination of active segments of an IDO inhibitor and a NAMPT inhibitor is adopted so as to obtain the furazan kind IDO/NAMPT double target inhibitor. On one hand, the furazan kind IDO/NAMPT double target inhibitor is capable of realizing dual inhibition of NAD biosynthesis, and possesses higher anti-tumor inhibition activity, and one the other hand, inhibition of IDO activity is capable of promoting T cell propagation effectively, so that the impurity of bodies on tumor cell attacks is improved. The furazan kind IDO/NAMPT double target inhibitor or the pharmaceutical compositions of the furazan kind IDO/NAMPT double target inhibitor are promising in application prospect, and are promising to be developed into anti-tumor drugs.
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Page/Page column 98; 99
(2018/10/19)
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- 2,2-dimethylbenzopyran derivative and preparation method and use thereof
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The invention belongs to the technical field of medicines, and discloses a 2,2-dimethylbenzopyran derivative and a preparation method and use of the 2,2-dimethylbenzopyran derivative. The derivative and pharmaceutically acceptable salt of the derivative have the structural formulae shown in the description, wherein Ar, Ar, X, Y and R1 are as described in the claims and the description. The preparation methods of the derivative and the pharmaceutically acceptable salt of the derivative comprise the following steps: the formula (I) is obtained by mainly taking acetaminophen as a raw material, and subjected to the reactions of Williamson ether formation, cyclization, hydrolysis, amide formation and the like; the formula II is obtained by mainly taking p-hydroxybenzaldehyde as a raw material, and subjected to the reactions of the Williamson ether formation, cyclization, Knoevenagel condensation, amide formation and the like. The derivative and the pharmaceutically acceptable salt ofthe derivative disclosed by the invention can be used for preparing neuroprotective agents and have better neuroprotective effects on ischemic stroke.
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Page/Page column 13; 14
(2019/01/16)
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- Synthesis and evaluation of N-heteroaromatic ring-based analogs of piperlongumine as potent anticancer agents
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Piperlongumine (PL) selectively targets a wide spectrum of cancer cells and induces their death by triggering various pathways, including apoptosis, necrosis and autophagy. However, the poor solubility is a serious concern for intensive study and clinical application. We synthesized its analogs 1–9 by replacement of the trimethoxyphenyl of PL with an N-heteroaromatic ring and/or not introduction of 2-Cl. These compounds improved aqueous solubility and displayed potent anticancer activity. The most active compound 9 selectively enhanced ROS levels in colon cancer cells and inhibited the cell proliferation but sparing non-tumor colon cells. Importantly, 9 significantly repressed tumor growth in an HCT-116 xenograft mouse model, suggesting that these N-heteroaromatic ring-based analogs of PL warrant further investigation.
- Zou, Yu,Yan, Chang,Zhang, Huibin,Xu, Jinyi,Zhang, Dayong,Huang, Zhangjian,Zhang, Yihua
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p. 313 - 319
(2017/07/07)
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- Palladium-Catalyzed Two-Component Domino Coupling Reaction of (Z)-β-Bromostyrenes with Norbornenes: Synthesis of 1,5-Enynes
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Polyfunctional molecules, 1,5-enynes, have been achieved via a palladium(0)-catalyzed domino coupling reaction of (Z)-β-bromostyrenes with norbornenes in the presence of cesium carbonate and N,N-dimethylformamide. The process involves a double Heck-type procedure, two-fold C(sp2) H activation and formation of two carbon-carbon bonds. There are possibilities of diversified transformation for the domino coupling of (Z)-β-bromostyrenes with norbornenes, the procedure is successfully driven to 1,5-enynes via accurate adjustment of the reaction conditions. (Figure presented.) .
- Mao, Jiangang,Li, Huifang,Wen, Herui,Li, Min,Fan, Xiaolin,Bao, Weiliang
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supporting information
p. 1873 - 1879
(2016/07/06)
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- 3-aryl acrylic acid and its derivatives viral anti-plant
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The invention relates to an application of 3-aryl acrylic acid represented by a general formula (I) and a derivative thereof in pesticides, wherein the 3-aryl acrylic acid and the derivative thereof can be adopted as novel anti-plant virus agents, can be provided for well inhibiting tobacco mosaic virus, pepper virus, tomato virus, sweet potato virus, potato virus, melon virus, maize dwarf mosaic virus and the like, and can be provided for effectively preventing and controlling virus diseases of a plurality of crops such as tobacco, pepper, tomato, melon vegetables, grains, vegetables, beans and the like, especially tobacco mosaic diseases. (Wherein Ar and R are defined in an instruction).
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Paragraph 0022; 0023
(2016/11/21)
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- Palladium(0)-catalyzed methylenecyclopropanation of norbornenes with vinyl bromides
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Highly strained methylenecyclopropane derivatives have been achieved via a novel and efficient Pd(0)-catalyzed domino reaction. The formal [2 + 1] cycloaddition reaction of vinyl bromides to norbornenes involves a Heck-type coupling and a C(sp2)-H bond activation.
- Mao, Jiangang,Bao, Weiliang
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supporting information
p. 2646 - 2649
(2014/06/09)
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- CYCLOPROPYL AMIDE DERIVATIVES
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The present invention relates to certain cyclopropyl amide compounds, pharmaceutical compositions comprising such compounds, and methods of treating cancer, including leukemias and solid tumors, inflammatory diseases, osteoporosis, atherosclerosis, irritable bowel syndrome, and other diseases and medical conditions, with such compounds and pharmaceutical compositions. The present invention also relates to certain cyclopropyl amide compounds for use in inhibiting nicotinamide phosphoribosyltransferase ("NAMPT").
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Paragraph 0170
(2014/05/24)
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- Fragment-based identification of amides derived from trans-2-(pyridin-3-yl) cyclopropanecarboxylic acid as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)
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Potent, trans-2-(pyridin-3-yl)cyclopropanecarboxamide-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using fragment-based screening and structure-based design techniques. Multiple crystal structures were obtained of initial fragment leads, and this structural information was utilized to improve the biochemical and cell-based potency of the associated molecules. Many of the optimized compounds exhibited nanomolar antiproliferative activities against human tumor lines in in vitro cell culture experiments. In a key example, a fragment lead (13, KD = 51 μM) was elaborated into a potent NAMPT inhibitor (39, NAMPT IC 50 = 0.0051 μM, A2780 cell culture IC50 = 0.000 49 μM) which demonstrated encouraging in vivo efficacy in an HT-1080 mouse xenograft tumor model.
- Giannetti, Anthony M.,Zheng, Xiaozhang,Skelton, Nicholas J.,Wang, Weiru,Bravo, Brandon J.,Bair, Kenneth W.,Baumeister, Timm,Cheng, Eric,Crocker, Lisa,Feng, Yezhen,Gunzner-Toste, Janet,Ho, Yen-Ching,Hua, Rongbao,Liederer, Bianca M.,Liu, Yongbo,Ma, Xiaolei,O'Brien, Thomas,Oeh, Jason,Sampath, Deepak,Shen, Youming,Wang, Chengcheng,Wang, Leslie,Wu, Hongxing,Xiao, Yang,Yuen, Po-Wai,Zak, Mark,Zhao, Guiling,Zhao, Qiang,Dragovich, Peter S.
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p. 770 - 792
(2014/03/21)
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- Design, synthesis and biological evaluation of benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of glycogen synthase kinase-3β (GSK-3β)
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Glycogen synthase kinase-3β (GSK-3β) plays a key role in type II diabetes and Alzheimer's diseases, to which non-ATP competitive inhibitors represent an effectively therapeutical approach due to their good specificity. Herein, a series of small molecules benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of GSK-3β have been designed and synthesized. The in vitro evaluation performed by luminescent assay showed most BTZ derivatives have inhibitory effects in micromolar scale. Among them compounds 6l, 6t and 6v have the IC50 values of 25.0 μM, 27.8 μM and 23.0 μM, respectively. Moreover 6v is devoid of any inhibitory activity in the assays to other thirteen protein kinases. Besides, SAR is analyzed and a hypothetical enzymatic binding mode is proposed by molecular docking study, which would be useful for new candidates design.
- Zhang, Peng,Hu, Hai-Rong,Bian, Shi-Hui,Huang, Zhao-Hui,Chu, Yong,Ye, De-Yong
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- Discovery of novel 4-anilinoquinazoline derivatives as potent inhibitors of epidermal growth factor receptor with antitumor activity
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Two new series of new compounds containing a 6-amino-substituted group or 6-acrylamide-substituted group linked to a 4-anilinoquinazoline nucleus have been discovered as potential EGFR inhibitors. These compounds proved efficient effects on antiproliferative activity and EGFR-TK inhibitory activity. Especially, N6-((5-bromothiophen-2-yl)methyl)-N4-(3- chlorophenyl)quinazoline-4,6-diamine (5e), showed the most potent inhibitory activity (IC50 = 3.11 μM for Hep G2, IC50 = 0.82 μM for A549). The EGFR molecular docking model suggested that the new compound is nicely bound to the region of EGFR, and cell morphology by Hoechst stain experiment suggested that these compounds efficiently induced apoptosis of A549 cells.
- Xu, Yun-Yun,Li, Si-Ning,Yu, Gao-Jian,Hu, Qing-Hua,Li, Huan-Qiu
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p. 6084 - 6091
(2013/09/23)
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- Tunable plastic films of a crystalline polymer by single-crystal-to-single- crystal photopolymerization of a diene: Self-templating and shock-absorbing two-dimensional hydrogen-bonding layers
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Film review: Two amide-containing bisolefin monomers undergo solid-state polymerization (see example) through a [2+2] reaction in a single-crystal-to- single-crystal fashion. The transformation was favored by the self-templating and shock-absorbing nature of hydrogen-bonding layers. The pyridine-containing polymers were soluble and useful for making plastic films with considerable tensile strengths. Copyright
- Garai, Mousumi,Santra, Ramkinkar,Biradha, Kumar
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supporting information
p. 5548 - 5551
(2013/06/27)
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- The design, synthesis and in vitro immunosuppressive evaluation of novel isobenzofuran derivatives
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The synthesis and biological evaluation of a series of novel isobenzofuran-based compounds are described. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and IMPDH type II inhibitor activity in vitro, as well as their structure-activity relationships were assessed. Several compounds demonstrated highly efficacious immunosuppressive properties, especially compounds 2d, 2e, 2h and 2j, which were superior to MPA, while compounds 2k, 2m, 2n, 4c and 5d exhibited an equipotent inhibitory activity compared to MPA. Generally, it was obviously demonstrated that α,β-unsaturated amides proved more potent than the diamide and urea series. The present study provides a guide for further research on development of safe and effective immunosuppressive agents.
- Yang, Na,Wang, Qing-He,Wang, Wen-Qian,Wang, Jian,Li, Feng,Tan, Shen-Peng,Cheng, Mao-Sheng
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body text
p. 53 - 56
(2012/02/16)
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- Synthesis and biological evaluation of N-(aminopyridine) benzamide analogues as histone deacetylase inhibitors
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A series of benzamide-based histone deacetylases (HDACs) inhibitors possessing N-(aminopyridine) residue as the zinc binding site of HDAC were synthesized and evaluated. Among these derivatives, compounds with N-(2-amino-4-pyridine) benzamide moiety have been found as the most potent ones. Moreover, introduction of appropriate substituents on the terminal aryl group acting as the surface-recognition domain could significantly improve the antiproliferative activity. In particular, the compound 4k possessed favorable pharmacokinetic characteristics and exhibited potent antitumor activity on xenograft model in mice at well tolerated doses, thus suggesting a good therapeutic index.
- Zhang, Qing-Wei,Li, Jian-Qi
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experimental part
p. 535 - 540
(2012/05/04)
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- Design, synthesis and biological evaluation of novel acrylamide analogues as inhibitors of BCR-ABL kinase
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A series of acrylamide analogues were designed and synthesized from Imatinib and Nilotinib as novel BCR-ABL inhibitors by application of the principle of nonclassical electronic isostere. All new compounds were evaluated for their inhibitory effects on the activity of BCR-ABL kinase and the proliferation of K562 leukemia cancer cells in vitro. The acrylamide analogues in which the substituent in C ring was trifluoromethyl group were identified as highly potent BCR-ABL kinase inhibitors. Compound 13f exhibited an IC 50 value as low as 20.6 nM in ABL kinase inhibition and an IC 50 value of 32.3 nM for antiproliferative activity, about 10.5-fold and 12-fold lower than those of Imatinib respectively. These results suggest that compound 13f is a promising candidate as a novel BCR-ABL kinase inhibitor for further development.
- Li, Shuxin,Yao, Zhenglin,Zhao, Yanjin,Chen, Wei,Wang, Huijia,Kuang, Xianzhao,Zhan, Wenhu,Yao, Shan,Yu, Shanyou,Hu, Wenxiang
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scheme or table
p. 5279 - 5282
(2012/09/07)
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- ACRYLAMIDE DERIVATIVES AS VANILLOID RECEPTOR 1 MODULATORS
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There are provided cynnamide derivatives of the compounds of the formula (I): which may be used as vanilloid receptor 1 modulators. Various related methods, formulations, variants, and embodiments are provided.
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Page/Page column 13-14
(2009/09/05)
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- Competitive formation of β-amino acids, propenoic, and ylidenemalonic acids by the Rodionov reaction from malonic acid, aldehydes, and ammonium acetate in alcoholic medium
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The Rodionov reaction of 49 available aliphatic and aromatic aldehydes with malonic acid and ammonium acetate in alcoholic medium, resulting in formation of β-amino acids, propenoic, and ylidenemalonic acids, was studied. Certain regioselectivity regularities of the reaction were revealed. Among the variety of ketones studied, cyclohexanone is the only whose reaction yields a β-amino acid. Unusual dehydrofluorination of 6-chloro-2-fluorocinnamic acid under the Rodionov reaction was discovered. 2005 Pleiades Publishing, Inc.
- Lebedev,Lebedeva,Sheludyakov,Kovaleva,Ustinova,Kozhevnikov
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p. 1113 - 1124
(2007/10/03)
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- KOH-promoted reaction of C,O,O-tris(trimethylsilyl) ketene acetal with aldehydes: Practical and easy access to (E)-α,β-ethylenic carboxylic acids
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The use of a catalytic amount of KOH has been found to be very efficient in promoting reaction of silylketene acetal 1 with aldehydes 2 to afford the corresponding (E)-α,β-ethylenic carboxylic acids 3 under very mild conditions.
- Lensen,Mouelhi,Bellassoued
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p. 1007 - 1011
(2007/10/03)
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- Two-carbon homologation of aldehydes via silyl ketene acetals: A new stereoselective approach to (E)-alkenoic acids
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Aldehydes are converted into (E)-α,β-unsaturated carboxylic acids using C,O,O-tris(trimethylsilyl)ketene acetal 1. This organosilicon reagent is easily generated from trimethylsilyl acetate, LDA, and chlorotrimethylsilane. The effectiveness of the reaction has been explored for a large variety of aldehydes with Lewis acids and fluorides as catalysts.
- Bellassoued, Moncef,Lensen, Nathalie,Bakasse, Mina,Mouelhi, Sinda
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p. 8785 - 8789
(2007/10/03)
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- EFFECT OF SUBSTITUENTS OF THE 1H AND 13C NMR CHEMICAL SHIFTS OF trans-PYRIDINEACRYLIC AND SUBSTITUTED trans-CINNAMIC ACIDS
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The principles of linear free energy relationships were applied to the 1H nmr and 13C nmr chemical shifts induced by substituents in three isomeric trans-pyridineacrylic and substituted trans-cinnamic acids.The data for the carboxy proton chemical shift correlated well with the simple Hammett equation.Taft's dual substituent parameter equation was used for the interpretation of the balance of the inductive and resonance effects through the ethylenic bond for the Cα and Cβ 13C nmr shift.Using the nuclear Overhauser method, the conformation of the carboxylic group in 2-pyridineacrylic acid was determined, and its unexpected behaviour in both 1H nmr chemical shifts and in the previously studied reaction with diazodiphenylmethane was interpreted by the increased electron density in the ?-electronic system favoured by the orbital symmetry of the part of the acid molecule.
- Jovanovic, Bratislav,Misic-Vukovic, Milica,Drmanic, Sasa,Csanadi, Janos
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p. 1495 - 1502
(2007/10/02)
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- Symmetry-Based Inhibitors of HIV Protease. Structure-Activity Studies of Acylated 2,4-Diamino-1,5-diphenyl-3-hydroxypentane and 2,5-Diamino-1,6-diphenylhexane-3,4-diol
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The structure-activity relationships in two series of novel, symmetry-based inhibitors of HIV protease, the enzyme responsible for maturation of the human immunodeficiency virus, are described.Beginning with lead compounds 3-6, the effect of adding polar, heterocyclic end groups to one or both ends of the symmetric or pseudosymmetric inhibitors was probed.Aqueous solubility was enhanced >1000-fold while maintaining potent inhibition of purified HIV-1 protease and anti-HIV activity in vitro.Pharmacokinetic studies in rats indicated a substantial difference in the absorption properties of mono-ol-based and diol-based inhibitors.The oral bioavailability of inhibitor 19 in rats was 19percent; however, the Cmax obtained failed to exceed the anti-HIV EC50 in vitro.Substantial plasma levels of potent inhibitors of the diol class were not obtained after oral administration in rats; however, the optimal combination of aqueous solubility and in vitro antiviral activity of several inhibitors support their potential use in intravenous therapy.
- Kempf, Dale J.,Codacovi, Lynnmarie,Wang, Xiu Chun,Kohlbrenner, William E.,Wideburg, Norman E.,et al.
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p. 320 - 330
(2007/10/02)
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- Isocytosine H2-receptor histamine antagonists II. Synthesis and evaluation of biological activity at histamine H1- and H2-receptors of 5-(heterocyclyl)methylisocytosines
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A series of 2--4-pyrimidones was synthesized based on oxmetidine 2, in which the methylenedioxyphenyl group of 2 was replaced by a heterocyclic ring.Good H2-receptor antagonist activity was retained over a range of basic and neutral heterocyclic substituents.Replacement of the 5-methyl-4-imidazolyl ring in selected compounds with 2-thiazolyl and, particularly, 3-bromo-2-pyridyl rings gave a series of compounds which have both H1- and H2-receptor histamine antagonist activities.Some structure-activity and structure-toxicity correlations are discussed.Compound 6d, 2--5-(6-methylpyrid-3-yl)-4-pyrimidone, has the most favourable combination of properties for H2-antagonism and has been evaluated further as an anti-secretory agent.
- Brown, Thomas H.,Blakemore, Robert C.,Blurton, Peter,Durant, Graham J.,Ganellin, C. Robin,et al.
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- Synthesis of 3-Methyl-5,6-dihydro-3H-benzofuroisoquinolin-7(7aH)-ones
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The coupling of 2-(alkoxymethoxy)phenylcopper derivatives with the salt of ethyl chloroformate and ethyl 3-(pyridin-3-yl)propenoate was found to be an efficient method for the preparation of 4-(2-hydroxyphenyl)pyridines 13 substituted at C-3 with a propanoate side chain.N-Methylation and O-alkylation with ethyl bromoacetate gave salts 3 which when treated with base underwent an intramolecular enolate addition to the pyridinium nucleus to produce spiro 4.Prolonged base treatment of 4 yielded ethyl 3-methyl-7-hydroxy-5,7a-dihydro-3H-benzofuroisoquinoline-6-carboxylates 5 by a Dieckmann reaction.Reduction of 5 led to predominately trans-3-methylhexahydro-1H-benzofuroisoquinolin-7(7aH)-ones, while reduction of 4 and then Dieckmann cyclization yielded mainly the cis isomers.
- Weller, Dwight D.,Stirchak, Eugene P.,Weller, Doreen L.
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p. 4597 - 4605
(2007/10/02)
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