- Synthesis, antiproliferative activity and DNA binding study of mixed ammine/cyclohexylamine platinum(II) complexes with 1-(substituted benzyl) azetidine-3, 3-dicarboxylates
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A novel series of ammine/cyclohexylamine platinum(II) complexes with 1-(substituted benzyl) azetidine-3, 3-dicarboxylates as leaving groups have been synthesized and characterized. All complexes were characterized by elemental analysis, IR, 1H NMR, and ESI-MS spectra. The in vitro antiproliferative activities of the platinum-based compounds have been investigated against several human cancer cell lines, indicating that complexes 1 and 11 showed comparable cytotoxicity to those of cisplatin and oxaliplatin against four cell lines, superior to that of carboplatin. The results of drug safety evaluation (acute toxicity study) showed that complex 11 was much less toxic than cisplatin and oxaliplatin. Flow cytometry and agarose gel electrophoresis studies revealed that both complexes 1 and 11 induced apoptosis of tumor cells and demonstrated the binding affinity of complexes with pET22b plasmid DNA.
- Sun, Yanyan,Gou, Shaohua,Yin, Runting,Jiang, Pingyuan
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Read Online
- ISOXAZOLE CARBOXAMIDE COMPOUNDS AND USES THEREOF
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A compound of Formula (I) or or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating hearing loss or balance disorder: Formula (I) wherein R1 and Y are as defined herein.
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Page/Page column 55-56
(2020/04/25)
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- Novel intermediate and improved process for the preparation of iobitridol using thereof
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The present invention relates to a novel method for producing iobitridol represented by chemical formula 1, 1-N,3-N-bis(2,3-dihydroxypropyl)-5-[3-hydroxy-2-(hydroxymethyl)propanamido]-2,4,6-triiodo-1-N,3-N-dimethylbenzene-1,3-dicarboxamide, which is a component for a contrast medium, and novel intermediates for the same. According to the present invention, desired entecavir can be produced economically and easily from the novel intermediates at a high yield.COPYRIGHT KIPO 2018
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Paragraph 0046; 0084-0086
(2018/04/18)
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- Targeting Alzheimer's disease by investigating previously unexplored chemical space surrounding the cholinesterase inhibitor donepezil
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A series of twenty seven acetylcholinesterase inhibitors, as potential agents for the treatment of Alzheimer's disease, were designed and synthesised based upon previously unexplored chemical space surrounding the molecular skeleton of the drug donepezil, which is currently used for the management of mild to severe Alzheimer's disease. Two series of analogues were prepared, the first looking at the replacement of the piperidine ring in donepezil with different sized saturated N-containing ring systems and the second looking at the introduction of different linkers between the indanone and piperidine rings in donepezil. The most active analogue 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (67) afforded an in vitro IC50value of 0.03 ± 0.07 μM against acetylcholinesterase with no cytotoxicity observed (IC50of >100 μM, SH-SY5Y cell line). In comparison donepezil had an IC50of 0.05 ± 0.06 μM and an observed cytotoxicity IC50of 15.54 ± 1.12 μM. Molecular modelling showed a strong correlation between activity and in silico binding in the active site of acetylcholinesterase.
- van Greunen, Divan G.,Cordier, Werner,Nell, Margo,van der Westhuyzen, Chris,Steenkamp, Vanessa,Panayides, Jenny-Lee,Riley, Darren L.
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p. 671 - 690
(2017/02/10)
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- Synthesis of Panal Terpenoid Core
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Panal is a natural bicyclic cadalane-type sesquiterpenoid with an unusual combination of stereocenters. It was isolated in 1988 as an alleged biosynthetic precursor of luciferin (a light-emitting molecule) in a bioluminescent fungus Panellus stipticus. Herein we present the first approach to the synthesis of the terpenoid skeleton of panal, which includes construction of five stereocenters, one of which is easily epimerizable. The key steps in the synthetic approach presented are high-pressure Diels-Alder reaction disobeying the ‘endo rule’, Barbier reductive allylation, and cyclization of trans-decalin ring via ring-closing metathesis.
- Baranov, Mikhail S.,Kaskova, Zinaida M.,Gritсenko, Roman,Postikova, Svetlana G.,Ivashkin, Pavel E.,Kislukhin, Alexander A.,Moskvin, Dmitrii I.,Mineev, Konstantin S.,Arseniev, Alexander S.,Labas, Yulii A.,Yampolsky, Ilia V.
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supporting information
p. 583 - 588
(2017/03/11)
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- Design, synthesis and biological evaluation of palladium (II) complexes with 1-(substituted benzyl) azetidine-3,3-dicarboxylates as leaving group
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A series of palladium complexes with 2,2′-bipyridine and 1-(substituted benzyl) azetidine-3, 3-dicarboxylates as ligands were synthesized and characterized by IR, 1H-NMR, ESI-MS spectra and elemental analysis. The in vitro cytotoxicity assays were carried out against A549, HCT-116, HepG-2 and SGC7901 cancer cell lines. The result showed that most of the complexes possessed moderate antiproliferative activity against HCT-116, HepG-2 and SGC7901 cell lines. Complex 12 (with 2,2′-bipyridine and 1-(3-methoxylbenzyl)azetidine-3,3-dicarboxylate as ligand) was the most potent antitumor agent among all thirteen complexes, which showed comparable or better cytotoxicity against all four tested cancer cell lines than carboplatin. The interaction between complex 12 and pET22b plasmid DNA was investigated by agarose gel electrophoresis, and the result of the study showed that complex 12 had no obvious interaction with the plasmid DNA.
- Xu, Gang,Lu, Hua,Zhitao, Jiang,Zhang, Shuying,Gou, Shaohua
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p. 701 - 707
(2015/11/28)
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- METHOD TO OBTAIN METHYLENE MALONATE VIA BIS(HYDROXYMETHYL) MALONATE PATHWAY
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Method to obtain methylene malonate and related monomers following a bis(hydroxymethyl) malonate pathway. A bis(hydroxymethyl) malonate intermediary is subsequently reacted (i.e., subjected to thermolysis) to provide a methylene malonate monomer species. A source of formaldehyde (e.g., formalin) is provided in the presence of a basic catalyst (e.g., calcium hydroxide), to which a malonate (e.g., diethyl malonate) is added under suitable reaction conditions to obtain the desired intermediary (e.g., dialkyl bis(hydroxymethyl) malonate). The intermediary is reacted (i.e., subjected to thermolysis) under suitable conditions in the presence of a suitable catalyst (e.g., a zeolite) to obtain a methylene malonate monomer. In an exemplary embodiment, the thermolysis reaction includes the addition of the bis(hydroxymethyl) malonate intermediary onto a heated catalyst. The reaction product is collected and purified. The disclosed methods may be performed in a continuous operation. Discrete steps may be performed by using modular units within a plant.
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Page/Page column 21; 22
(2014/07/23)
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- ANTIBACTERIAL AGENTS
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Antibacterial compounds of formula (I) are provided, as well as stereoisomers and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of such compounds.
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Page/Page column 55-56
(2013/12/03)
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- Synthesis and herbicidal activity of diphenyl ether derivatives containing unsaturated carboxylates
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A series of novel diphenyl ether derivatives containing unsaturated carboxylates were designed and synthesized. Their structures were identified by 1H nuclear magnetic resonance and elemental analyses. The bioassays indicated that the compounds 5b and 5c exhibited good herbicidal activities against velvetleaf at a concentration of 30-40 g/hm2. The relationship between structure and herbicidal activity was also discussed. Among unsaturated carboxylates group, butenoate is the most promising one. Amonst them, 4-ethoxy-4-oxobutenyl 5-(2-chloro-4-(trifluoromethyl)phenoxy)-2- nitrobenzoate 5b was identified as the most promising candidate due to its high protoporphyrinogen IX oxidase inhibition effect (pI50 = 6.64) and good herbicidal activity against broadleaf weeds with selectivity to soybean and low toxicity to mammals.
- Yu, Haibo,Yang, Huibin,Cui, Dongliang,Lv, Liang,Li, Bin
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scheme or table
p. 11718 - 11726
(2012/04/04)
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- The chemical development and scale-up of sampatrilat
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The discovery and scale-up of two routes to sampatrilat are described. The first Chemical R and D route used a side product from another development project to accelerate drug supply and expedite the early development programme. The second, more efficient Chemical R and D route had the potential for commercialisation and used an environmentally friendly variant of the Baylis-Hillman reaction, and an asymmetric Michael addition as key steps. Full preparative details for the aminomethacrylate 4, a potentially useful chiral synthon, are given for the first time, along with full experimental details of the asymmetric Michael addition to make the chiral glutarate 5. Finally, a striking polymorph case history is described.
- Dunn, Peter J.,Hughes, Michael L.,Searle, Patricia M.,Wood, Albert S.
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p. 244 - 253
(2013/09/06)
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- Synthetic studies on azadirachtin: Construction of the highly functionalized decalin moiety of azadirachtin
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Construction of the left segment of azadirachtin in naturally occurring enantiomer is described. The key reaction is an intramolecular Diels-Alder reaction, which was performed under thermal conditions to afford the highly functionalized decalin compounds selectively.
- Ishihara, Jun,Yamamoto, Yuuko,Kanoh, Naoki,Murai, Akio
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p. 4387 - 4390
(2007/10/03)
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- Bis(hydroxymethylation) of the active methylene group of 1,3-Dicarbouyl and related compounds
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Treatment of dialkyl and di(aralkyl) malonates, alkyl cyano- and acetoacetates, and 1,3-diketones with formaldehyde in the presence of tertiary amines gives their 2,2-bis(hydroxymethyl) derivatives in 59 to 96% yield.
- Guzaev,Lonnberg
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p. 1281 - 1284
(2007/10/03)
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- Synthesis of Oligonucleotide Analogues by Using Phosphoramidite Reagents Derived from 2,2-Bis(hydroxymethyl)malonates
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A new family of non-nucleosidic phosphoramidite reagents derived from either esters or amides of 2,2-bis(hydroxymethyl)malonic acid is described.The utility of the building blocks 1-5 is demonstrated by preparation of 5'-phosphorylated oligonucleotides as well as hydrophobic, polyamino and fluorescent labelled oligonucleotide analogues.
- Guzaev, Andrei,Salo, Harri,Azhaev, Alex,Lonnberg, Harri
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p. S226 - S229
(2007/10/03)
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- SYNTHESIS OF 5,5'-DIHYDROXYLEUCINE AND 4-FLUORO-5,5'-DIHYDROXYLEUCINE, THE REDUCTION PRODUCTS OF 4-CARBOXYGLUTAMIC AND 4-CARBOXY-4-FLUOROGLUTAMIC ACIDS
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Schemes for the synthesis of 5,5'-dihydroxyleucine 3 and its 4-fluoro analog 7 involving the condensation of a suitable 'aminoacid moiety' with 2,2-dimethyl-5-iodomethyl-1,3-dioxane 15D or its fluoro analog 27A were tested.The anion of the ethyl N-diphenylmethylene-glycinate 25 gave better yields of 3 than the classical anion of diethyl acetamidomalonate.This strategy could not be successfully applied to the synthesis of 7, which could be prepared by reduction of a suitably protected 4-fluoro-4-carboxyglutamate with BMS.
- Dubois, Joelle,Foures, Christine,Bory, Sonia,Falcou, Serge,Gaudry, Michel,Marquet, Andree
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p. 1001 - 1012
(2007/10/02)
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- Structure-activity relationship of miltirone, an active central benzodiazepine receptor ligand isolated from Salvia miltiorrhiza bunge (Danshen)
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Twenty one o-quinonoid-type compounds and one coumarin-type compound related to miltirone (1) have been synthesized with the aim to identify the key structural elements involved in miltirone's interaction with the central benzodiazepine receptor. On the basis of their inhibition of [3H]flunitrazepam binding to bovine cerebral cortex membranes, it is apparent that ring A of miltirone is essential for affinity. Although increasing the size of ring A from six-membered to seven- and eight-membered is well-tolerated, the introduction of polar hydroxyl groups greatly reduces binding affinity. The presence of 1,1-dimethyl groups on ring A is, however, not essential. On the other hand, the isopropyl group on ring C appears to be critical for binding as its removal decreases affinity by more than 30-fold. It can, however, be replaced with a methyl group with minimal reduction in affinity. Finally, linking ring A and B with a -CH2CH2- bridge results in analogue 89, which is 6 times more potent than miltirone at the central benzodiazepine receptor (IC50 = 0.05 μM).
- Chang,Chui,Tan,Yang,Zhong,Lee,Sham,Wong
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p. 1675 - 1692
(2007/10/02)
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- Malonate-based light stabilizers for plastics
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Malonate-derived acetal esters and amides possessing the polyalkyl piperidin-4-yl moiety are useful light stabilizers with synthetic polymer resins such as polyolefins and, in particular, polypropylene.
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