- Homocam ptothecin 5-ene norcantharidin acid ester derivative, and regioselective synthesis method thereof
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The invention discloses a homocam ptothecin 5-ene norcantharidin acid ester derivative represented by fomula I, and a regioselective synthesis method thereof, wherein R is selected from C1-C6 alkyl, substituted alkyl, and cycloalkyl. It is confirmed by activity test that the homocam ptothecin 5-ene norcantharidin acid ester derivative I possesses excellent anti-tumor effect, and is especially highin inhibition activity on liver cancer, stomach cancer, colorectal carcinoma and pancreas cancer. According to the preparation method of the homocam ptothecin 5-ene norcantharidin acid ester derivative, the raw materials are easily available; cost is low; synthesis reaction regioselectivity is extremely high; target product yield is high; and preparation is convenient.
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Paragraph 0025-0029
(2019/11/21)
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- Homocamptothecin norcantharidinate derivative, and regioselective synthesis method thereof
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The invention provides a homocamptothecin norcantharidinate derivative I and a regioselective synthesis method thereof in the fields of design and synthesis of novel drugs. The homocamptothecin norcantharidinate derivative I has a structural formula as shown in a formula I which is described in the specification. In the formula I, R is selected from the group consisting of C1-C6 alkyl, substitutedalkyl and cycloalkyl groups. Activity test results prove that the homocamptothecin norcantharidinate derivative I designed and synthesized by using the method provided by the invention has good antitumor effect, and specifically has high activity on liver cancer, gastric cancer, colon cancer and pancreatic cancer. In addition, the method for preparing the homocamptothecin norcantharidinate derivative I provided by the invention has the advantages of easily-available raw materials, low cost, extremely-high synthesis reaction regioselectivity and high target product yield; and the homocamptothecin norcantharidinate derivative I provided by the invention is easy to be prepared.
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Paragraph 0025; 0028-0029
(2019/11/21)
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- Synthesis and structure-activity relationship study of novel 3-heteroarylcoumarins based on pyridazine scaffold as selective MAO-B inhibitors
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Compounds of hybrid structure pyridazine-coumarin were discovered as potent, selective and reversible inhibitors of monoamine oxidase B (MAO-B). These compounds were synthesized in good yield following a multistep approach based on Knoevenagel reaction and using as key intermediate pyridazinone 16, which was obtained from maleic anhydride and furan. Compounds 9b and 9d are the most active compounds of these series, with IC50 values in the sub-micromolar range, and lack of cytotoxic effects. Theoretical calculation of ADME properties also suggested a good pharmacokinetic profile for both compounds. Docking simulations provided insights into enzyme inhibitor interactions and allowed us to rationalize the observed structure-activity relationships (SARs).
- Costas-Lago, María Carmen,Besada, Pedro,Rodríguez-Enríquez, Fernanda,Vi?a, Dolores,Vilar, Santiago,Uriarte, Eugenio,Borges, Fernanda,Terán, Carmen
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supporting information
p. 1 - 11
(2017/08/10)
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- Diacetylene-Based C 2h-Symmetric Monomers for Two-Dimensional-Polymer Synthesis
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Two linear monomers with two terminal photoreactive groups (anthracene or maleimide) embedded in a diacetylene skeleton were synthesized for two-dimensional-polymer synthesis. Both of them were crystallized and their single-crystal structures were solved. It was found that the size of terminal groups can be critical for diacetylene's arrangement. The crystal structure of dimaleimide monomer revealed that maleimide groups strongly stacking in antiparallel and the photo-induced [2+2] cycloaddition of stacked maleimides was preliminary studied.
- Song, Mengyao,Ma, Hanbing,Ren, Minghan,Ai, Zhaoquan,Li, Ming
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supporting information
p. 445 - 450
(2017/02/24)
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- Albumin-polymer conjugate nanoparticles and their interactions with prostate cancer cells in 2D and 3D culture: Comparison between PMMA and PCL
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Using proteins as the hydrophilic moiety can dramatically improve the biodegradability and biocompatibility of self-assembled amphiphilic nanoparticles in the field of nanomedicine. In this study, we fabricated and evaluated curcumin loaded albumin-polycaprolactone nanoparticles as a novel drug delivery system for prostate carcinoma therapeutics and compared their performance to poly(methyl methacrylate) (PMMA), a non-degradable and amorphous polymer. The maleimide functionalized poly(ε-caprolactone) (PCL) was obtain using ring opening polymerization (ROP) of ε-caprolactone where N-(2-hydroxyethyl)maleimide was used as an initiator. The resorbable albumin-polymer conjugate was prepared by conjugating the hydrophobic maleimide-terminated PCL to the hydrophilic bovine serum albumin (BSA) via a simple Michael addition reaction. PMMA was conjugated in a similar manner. The amphiphilic BSA-polymer conjugates can self-assemble into nanoparticles, displaying well-defined structure, prolonged storage stability, and excellent biocompatibility. The BSA nanoparticles, with encapsulated curcumin, exhibited highly enhanced antitumor activity compared to free curcumin. Furthermore, the high efficacy of the curcumin loaded nanoparticles was verified by effectively inhibiting the growth of three-dimensional LNCaP multicellular tumour spheroids. The cytotoxicity was attributed to the efficient cellular uptake of the nanoparticles through caveolic endocytosis. The direct comparison between PCL and the PMMA revealed that drug loading and release as well as cytotoxicity is not significantly affected by the nature of the polymer. However, it seems that nanoparticles based on PMMA penetrate quicker into LNCaP multicellular tumour spheroids thanks to the increased stability. The faster penetration was found to reduce the toxicity of the nanoparticles as evidenced by the lower number of dead cells. In contrast, the fully degradable PCL-based nanoparticles were more efficient in delivering the drug, thus limiting the growth of LNCaP multicellular tumour spheroids.
- Jiang, Yanyan,Lu, Hongxu,Dag, Aydan,Hart-Smith, Gene,Stenzel, Martina H.
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p. 2017 - 2027
(2016/03/22)
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- Norcantharidin monomer-acid monoester derivative and anti-tumor application thereof
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The invention provides a norcantharidin monomer-acid monoester derivative and an application thereof. The structural formula of the derivative is shown as the No.3 formula (please see the specification), wherein R is selected from alkyl or benzyl of C1 to C3. An activity test proves that the third designed and synthesized norcantharidin monomer-acid monoester derivative has good inhabitation activity in liver cancer tumor cells, stomach cancer tumor cells and colon cancer tumor cells, and can be expected to be applied to preparing medicine for resisting the three tumors.
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Paragraph 0027; 0029; 0030
(2017/07/19)
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- New Dielectric Elastomers with Variable Moduli
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Dielectric elastomers have been widely investigated for muscle-like soft actuators and capacitive sensors. Mechanical properties play a central role in the performances of the active material. Most elastomers have specific moduli pre-determined by the polymers' molecular structures, which are not suitable for applications in changing working conditions as natural muscles are capable of. Here new dielectric elastomers are described exhibiting variable moduli controlled via thermal treatment. The elastomers contain furan-maleimide Diels-Alder adduct moieties to administer the crosslinking densities of the elastomeric networks via reversible Diels-Alder/retro-Diels-Alder cycloaddition reaction, resulting in changes in the elastomers' moduli. One of the synthesized elastomers has moduli that can be controlled between 0.17 and 0.52 MPa incrementally and reversibly. Capacitive strain sensors based on this elastomer can be operated in both rigid and soft modes to achieve variable sensing response up to 30% linear strain. Actuators were fabricated and operated in both high strain mode (35% actuation area strain at 65 MV m-1) and high force output mode (0.55 MPa at 104 MV m-1). The elastomers can exhibit a range of stress-strain outputs in similar fashion as muscle.
- Hu, Wei,Ren, Zhi,Li, Junpeng,Askounis, Erin,Xie, Zhixin,Pei, Qibing
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p. 4827 - 4836
(2015/08/18)
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- Albumin-micelles via a one-pot technology platform for the delivery of drugs
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A new micelle delivery platform based on albumin coated nanoparticles is able to selectively deliver the payload to cancerous cells while healthy cells remain less affected. The technology is simple and can be used in a one-pot procedure. the Partner Organisations 2014.
- Jiang, Yanyan,Liang, Mingtao,Svejkar, Domenic,Hart-Smith, Gene,Lu, Hongxu,Scarano, Wei,Stenzel, Martina H.
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supporting information
p. 6394 - 6397
(2014/06/09)
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- NANOPARTICLES FOR DRUG DELIVERY COMPRISING ALBUMIN HAVING A POLYMER CHAIN COUPLED THERETO
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The invention provides a dispersion of assemblies. The assemblies comprise an albumin derivative comprising albumin having a polymer chain coupled thereto, wherein the assemblies comprise a core comprising the polymer chains and a shell comprising the albumin. A process for making the dispersion and methods of using the dispersion are also described.
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Paragraph 000130
(2014/10/18)
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- DENTAL MATERIALS BASED ON MONOMERS HAVING DEBONDING-ON-DEMAND PROPERTIES
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The invention relates to a dental restorative material which comprises a thermolabile or photolabile polymerizable compound of Formula I: [(Z1)m-Q1-X)]k-T-[Y-Q2-(Z2)n]1??Formula I, in which T represents a thermolabile or photolabile group, Z1 and Z2 in each case independently represent a polymerizable group selected from vinyl groups, CH2═CR1—CO—O— and CH2═CR1—CO—NR2— or an adhesive group selected from —Si(OR)3, —COOH, —O—PO(OH)2, —PO(OH)2, —SO2OH and —SH, wherein at least one Z1 or Z2 is a polymerizable group, Q1 in each case independently is missing or represents an (m+1)-valent linear or branched aliphatic C1-C20 radical which can be interrupted by —O—, —S—, —CO—O—, —O—CO—, —CO—NR3—, —NR3—CO—, —O—CO—NR3—, —NR3—CO—O— or —NR3—CO—NR3—, Q2 in each case independently is missing or represents an (n+1)-valent linear or branched aliphatic C1-C20 radical which can be interrupted by —O—, —S—, —CO—O—, —O—CO—, —CO—NR3—, —NR3—CO—, —O—CO—NR3—, —NR3—CO—O— or —NR3—CO—NR3—, X and Y in each case independently are missing or represent —O—, —S—, CO—O—, —O—CO—, —CO—NR3—, —NR3—CO—, —O—CO—NR3—, —NR3—CO—O— or —NR3—CO—NR3—, R, R1, R2 and R3 in each case independently represent H or a C1-C7 alkyl radical and k, l, m and n in each case independently are 1, 2 or 3.
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Paragraph 0141; 0142; 0143; 0144
(2014/11/13)
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- Thermoreversible reactions on inorganic nanoparticle surfaces: Diels-alder reactions on sterically crowded surfaces
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Organically surface-functionalized nanoparticles are important cross-linkers for nanocomposites. In the past, many cross-linking reactions were based on simple radical additions. However, novel smart materials require reversible reactions. These reactions, such as the Diels-Alder reaction, often have a specific sterical demand, e.g., a six-centered transition state. In this study, 5 nm silica particles were functionalized with maleimide groups, and their reactivity with regard to Diels-Alder reactions were investigated, applying various techniques. A new method for the surface modification of silica nanoparticles is presented, minimizing agglomeration in organic solvents and thus increasing the accessibility of the functional groups on the particle surface. Kinetic studies of substituted model compounds were carried out to evaluate the reactivity of the maleimide functionality. The Diels-Alder reaction between 2,5-dimethylfuran and N-propylmaleimide, N-ethyl(N-propylcarbamato) maleimide, and N-phenylmaleimide was followed by UV/Vis spectroscopy. The reaction rate increases in this order, showing the effect of maleimide substitution. Afterwards N-((3-triethoxysilyl)propyl)maleimide was used to graft maleimidopropyl functional groups onto the nanoparticle surface. 3-Aminopropyltriethoxysilane, which could then be reacted with 1,1′-(methylenedi-4,1-phenylene)bismaleimide, was used to attach phenyl-substituted maleimide functionality to the surface. 3- Isocyanatopropyltriethoxysilane introduced the electron-drawing carbamato functionality into the system. The surface coverage of the samples was characterized applying CHN analysis, TGA-FTIR coupling, and FTIR spectroscopy. All analytical methods revealed that the functional groups are covalently bonded to the silica surface and the maleimide rings remain intact. Diels-Alder reactions of the surface groups show that the reactivity of the molecules attached to the particles depends on sterical crowding, but the reaction rate is not significantly changed by surface effects.
- Engel, Tom,Kickelbick, Guido
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p. 149 - 157
(2013/08/24)
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- Multifunctional Giant Amphiphiles via simultaneous copper(i)-catalyzed azide-alkyne cycloaddition and living radical polymerization
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A novel class of chemically addressable, multifunctional Giant Amphiphiles was synthesized in excellent yields and polydispersity following simultaneous or sequential living radical polymerization and the click, copper(i)-catalysed azide-alkyne cycloaddition (CuAAC). This new approach allows chemical tailoring of the biomacromolecules and in situ formation of nanocontainers.
- Daskalaki, Eleftheria,Le Droumaguet, Benjamin,Gerard, David,Velonia, Kelly
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supporting information; experimental part
p. 1586 - 1588
(2012/03/11)
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- Norcantharidin analogues with nematocidal activity in Haemonchus contortus
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With the major problems with resistance in parasitic nematodes of livestock to anthelmintic drugs, there is an urgent need to develop new nematocides. In the present study, we employed a targeted approach for the design of a series of norcantharidin analogues (n = 54) for activity testing against the barber's pole worm (Haemonchus contortus) of small ruminants in a larval development assay (LDA) and also for toxicity testing on nine distinct human cell lines. Although none of the 54 analogues synthesized were toxic to any of these cell lines, three of them (N-octyl-7-oxabicyclo(2.2.1)heptane-2,3-dicarboximide (B2), N-decyl-7-oxabicyclo(2.2.1)heptane-2,3-dicarboximide (B3) and 4-[(4-methyl)-3-ethyl-2-methyl-5-phenylfuran-10-oxa-4-azatricyclo[5.2.1] decane-3,5-dione (B21) reproducibly displayed 99-100% lethality to H. contortus in LDA, with LD50s of 25-40 μM. The high 'hit rate' (5.6%) indicates that the approach taken here has advantages over conventional drug screening methods. A major advantage of norcantharidin analogues over some other currently available anthelmintics is that they can be produced in one to two steps in large amounts at low cost and high purity, and do not require any additional steps for the isolation of the active isomer. This positions them well for commercial development.
- Campbell, Bronwyn E.,Tarleton, Mark,Gordon, Christopher P.,Sakoff, Jennette A.,Gilbert, Jayne,McCluskey, Adam,Gasser, Robin B.
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supporting information; experimental part
p. 3277 - 3281
(2011/07/07)
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- An experimental and theoretical study of stereoselectivity of furan-maleic anhydride and furan-maleimide Diels-Alder reactions
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The stereoselectivity of the reaction of furan (1) with maleic anhydride (2) and maleimide (3) was studied experimentally and theoretically. Although the two reactions are highly similar with regard to their preference for endo and exo steroisomers, notab
- Rulisek, Lubomir,Sebek, Pavel,Havlas, Zdenek,Hrabal, Richard,Capek, Pavel,Svatos, Ales
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p. 6295 - 6302
(2007/10/03)
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- Anhydride modified cantharidin analogues useful in the treatment of cancer
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Anhydride modified cantharidin analogues useful in the treatment of certain forms of cancer also methods for the screening for anti-cancer activity of these analogues and/or their ability to sensitise cancer cells to cancer treatment. The modified cantharidin analogues have structure (I) or (II), wherein R1, R2, R3 and R4 are H, aryl or alkyl; X is O, N or S; Y is O, S, NH, NR; R is alkyl or aryl; A and B are H or CH3; W and Z are CHOH or C=O. These compounds inhibit protein phosphatase. 1
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Page/Page column 5-6
(2008/06/13)
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- Clay-catalyzed solventless addition reactions of furan with α,β- unsaturated carbonyl compounds
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The reaction of furan with α,β-unsaturated carbonyl dienophiles catalyzed by K10 montmorillonite in the absence of organic solvents produces the corresponding Diels-Alder adducts and, in the case of methyl vinyl ketone, Michael-type products, under much milder conditions than the conventional protocols. The results are consistent with acid catalysis on the clay surface. Acrylates gave lower yields and/or decomposition products. The reaction can be extended to alkynic substrates such as DMAD to afford cycloadducts in good yields.
- Avalos, Martin,Babiano, Reyes,Bravo, Jose L.,Cintas, Pedro,Jimenez, Jose L.,Palacios, Juan C.
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p. 9301 - 9304
(2007/10/03)
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- EFFECT OF HIGH PRESSURE ON THE RATE CONSTANT OF THE DIELS-ALDER REACTION BETWEEN FURAN AND MALEIC ANHYDRIDE
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The effect of high pressure (up to 700 MPa) on the rate of the Diels-alder reaction between furan and maleic anhydride has been investigated in deuterated acetone at 20 deg C.The volume effect of the reaction at atmospheric pressure is found to be ΔV
- Zhulin, V. M.,Kel'tseva, M. V.,Bogdanov, V. S.,Koreshkov, Yu. D.,Kabotyanskaya, E. B.
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p. 456 - 459
(2007/10/02)
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- EFFECT OF HIGH PRESSURE ON THE COMPOSITION OF STEREOISOMERS OF THE DIELS-ALDER REACTION BETWEEN FURAN AND MALEIC ANHYDRIDE
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The kinetic data on the Diels-Alder reaction between furan and maleic anhydride at atmospheric pressure and 20 and 40 deg C correspond to a scheme of the process which includes transformation of an endo-isomer into an exo-isomer without preliminary decomp
- Zhulin, V. M.,Bogdanov, V. S.,Kel'tseva, M. V.,Kabotyanskaya, E. B.,Koreshkov, Yu. D.
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p. 2303 - 2308
(2007/10/02)
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