- Light-activated drug release from prodrug nanoassemblies by structure destruction
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We report here a novel light-triggered nanosystem based on co-assembling nanoaggregates (NAs) of lipophilic photosensitizers and lipophilic prodrugs containing multiple thioethers. Upon laser irradiation, the oxidization of the multiple thioethers by photosensitizer-generated singlet oxygen could rapidly destroy the NA structure, resulting in faster drug release than those containing a single thioether.
- Li, Yang,Wang, Shujuan,Huang, Yulan,Chen, Yuwen,Wu, Wenbi,Liu, Yu,Zhang, Jing,Feng, Yue,Jiang, Xian,Gou, Maling
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Read Online
- Design and Synthesis of Novel Oleanolic Acid-Linked Disulfide, Thioether, or Selenium Ether Moieties as Potent Cytotoxic Agents
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A series of novel oleanolic acid (OA)-linked disulfide, thioether, or selenium ether derivatives was synthesized, and their antiproliferative activity was evaluated against human liver cancer (BEL-7402 and HepG-2), colon cancer (HCT116), and normal liver (L02) cell lines using methyl thiazolyl tetrazolium assay (MTT). Preliminary bioassay results revealed that OA derivatives modified at the C3?OH position, i. e., compound a4 containing sulfide ether, exhibited the best antiproliferative activity against BEL-7402 cells, with an IC50 value of 5.70±0.82 μM. Further flow cytometry assays revealed that compound a4 exerted its antiproliferative effects by inducing cell cycle arrest in the G2/M phase leading to apoptosis. Moreover, compared with the lead compound OA and the positive control drug 5-fluorouracil (5-FU), the OA derivatives demonstrated potent antiproliferative activities against the cancer cell lines.
- Li, Ya-Mei,Liu, Chuan-Feng,Luan, Tian,Zhang, Yu
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- Preparation method of thioglycolic anhydride
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The invention discloses a preparation method of thioglycolic anhydride. The method comprises the following steps of: vaporization of trifluoroacetic anhydride: vaporizing trifluoroacetic anhydride ina vaporizing device for later use; synthesis of thioglycolic anhydride: preheating the interior of a suspended gas-solid reaction device to 45-65 DEG C, introducing the vaporized trifluoroacetic anhydride into the suspended-state gas-solid reaction device, intermittently adding thionyl diacetic acid from the top of the suspended-state gas-solid reaction device, reacting for 2 hours, stopping introducing the vaporized trifluoroacetic anhydride from a gas inlet, stopping heating, and leading out an obtained solid product from a discharging port; and purification of thioglycolic anhydride: washing the solid product with refrigerated anhydrous petroleum ether and anhydrous ether respectively to obtain pure thioglycolic anhydride. The thioglycolic anhydride synthesized by the method is high inpurity and high in yield; and the yield of erdosteine prepared by reacting the thioglycolic anhydride serving as a raw material with homocysteine thiolactone hydrochloride is high.
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Paragraph 0037-0052; 0060-0065
(2020/12/10)
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- Anti-tumor prodrug with P-glycoprotein inhibition function and preparation method
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The invention discloses an anti-tumor prodrug with a P-glycoprotein inhibition function and a preparation method. The prodrug comprises a part formed by covalently connecting an anti-tumor drug and polyethylene glycol vitamin E succinate through a connecting arm, wherein the connecting arm comprises a sensitive bond; the sensitive bond is a chemical bond which is broken in an oxidization or reduction environment. The free polyethylene glycol vitamin E succinate and the active anti-tumor drug are dissociated; the polyethylene glycol vitamin E succinate is combined with P-glycoprotein; the expression of a P-glycoprotein efflux pump is inhibited, the activity of the P-glycoprotein is inhibited, the excretion of the anti-tumor drug is reduced and the intracellular concentration of the drug isimproved, so that the multi-drug drug resisting property of tumor cells is inhibited, the intracellular concentration of the active anti-tumor drug is greatly improved and a remarkable anti-tumor effect is obtained. The released active drug can be combined with a specific target spot in the cells and the growth of the tumor cells is inhibited.
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Paragraph 0051; 0053
(2018/07/30)
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- Efficient cyclodehydration of dicarboxylic acids with oxalyl chloride
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Literature examples illustrating the use of oxalyl chloride to prepare dicarboxylic acid anhydrides are surprisingly limited. At the same time, we have discovered a method involving the use of this readily available reagent which allowed the preparation of novel cyclic anhydrides where other, more conventional, methods had failed. Herein, we demonstrate that the method is applicable to a wide diversity of substrates, delivers good to excellent yields of cyclic anhydrides without chromatographic purification and can be considered a synthetic tool of choice whenever dicarboxylic acid cyclodehydration is required.
- Kantin, Grigory,Chupakhin, Evgeny,Dar'in, Dmitry,Krasavin, Mikhail
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supporting information
p. 3160 - 3163
(2017/07/18)
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- Room-temperature synthesis of pharmaceutically important carboxylic acids bearing the 1,2,4-oxadiazole moiety
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An efficient and mild one-pot protocol has been developed for the synthesis of 1,2,4-oxadiazoles via the reaction of amidoximes with dicarboxylic acid anhydrides in a NaOH/DMSO medium. The method allows the synthesis of diversely substituted carboxylic acids bearing the 1,2,4-oxadiazole motif, – a popular building block for pharmaceutical research, in moderate to excellent yields. The reaction scope includes aromatic and heteroaromatic amidoximes as well as five-, six- and seven-membered anhydrides. The advantages of this procedure are proven gram-scalability and the use of inexpensive starting materials, which from a process chemistry point of view are essential for future industrial applications.
- Tarasenko, Marina,Duderin, Nikolay,Sharonova, Tatyana,Baykov, Sergey,Shetnev, Anton,Smirnov, Alexey V.
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supporting information
p. 3672 - 3677
(2017/08/23)
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- New Heterocyclic Product Space for the Castagnoli-Cushman Three-Component Reaction
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Significant expansion of heterocyclic product space accessible by the Castagnoli-Cushman reaction (CCR) has been achieved via the use of glutaric anhydride analogues containing endocyclic substitutions with oxygen, nitrogen, and sulfur. Incorporation of these heteroatoms in the anhydride's backbone results in enhanced reactivity and generally lower temperatures that are required for the reactions to go to completion. These findings are particularly significant in light of the CCR recently recognized as an efficient tool for lead-oriented synthesis.
- Dar'In, Dmitry,Bakulina, Olga,Chizhova, Maria,Krasavin, Mikhail
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supporting information
p. 3930 - 3933
(2015/08/18)
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- INHIBITOR OF PLASMINOGEN ACTIVATOR INHIBITOR-1
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The present invention relates to a novel compound having plasminogen activator inhibitor-1 (PAI-1) inhibitory activity, and a PAI-1 inhibitor comprising the compound as an active ingredient. The present invention further relates to a pharmaceutical compos
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Page/Page column 49
(2011/02/17)
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- BUPRENORPHINE DERIVATIVES AND USES THEREOF
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Ester derivatives of the phenolic hydroxyl group of buprenorphine are described that can be used in the treatment of opiate dependency and/or moderate to severe pain. The esters have an enhanced bioavailability, an enhanced duration of action, and a reduc
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Page/Page column 26
(2008/06/13)
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- Synthesis of new chiral sulfinyldiacetic acid derivatives and attempt at chemoselective asymmetric pummerer reaction
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(RS)-1 (85% ee) was prepared by utilizing a porcin pancreatic lipase-promoted hydrolysis of sulfinyldiacetic acid dimethyl ester (8) which was derived from thiodiacetic acid (7). (RS)-1 (99% ee) and (S S)-1 (99% ee) were r
- Nagao, Yoshimitsu,Miyamoto, Satoshi,Hayashi, Kazuhiko,Mihira, Ado,Sano, Shigeki
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p. 558 - 562
(2007/10/03)
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- Highly chemoselective Pummerer reactions of sulfinyldiacetic acid derivative
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Sulfinyldiacetic acid amide ester rac-1 was efficiently synthesized starting from thiodiacetic acid 4. Treatment of rac-1 with Ac2O and TMSOTf in CH2Cl2 at -40°C gave chemoselectively amide site α-acetoxy sulfide rac-2 in a ratio (91:9) of rac-2 and rac-3 and in a 90% total yield. Similar treatment of 1 with Ac2O and TMSOTf in DMF at room temperature furnished ester site α-acetoxy sulfide rac-3 in a highly chemoselective manner (rac-2:rac-3=3:97) and in a 92% total yield.
- Nagao, Yoshimitsu,Miyamoto, Satoshi,Hayashi, Kazuhiko,Mihira, Ado,Sano, Shigeki
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p. 1519 - 1522
(2007/10/03)
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- Synthesis and structure of macrocyclic dioxa-, dithia-, diazatetralactams and derivatives
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The high yield stepwise synthesis of 18-membered dioxa-, dithia- and diazatetralactams is described. The two key steps are: i) the dissymetrization of the reactivity of a diacid via its cyclic anhydride and ii) the activation-cyclization of the intermediate diamide diacid avoiding the high-dilution technique. Two series of diazatetralactam derivatives are prepared: bibranched compounds bearing various substituents and macrobicyclic or macrotricyclic species with phenantroline units. Tim main conformer of the dioxatetralactam was found by 13C nmr and molecular modelling to have a D2 symmetry while the dithiatetralactam in vacuo and the Boc substituted diazatetralactam in the solid state have a C2 symmetry.
- Cathala, Bernard,Raouf-Benchekroun, Khadija,Galaup, Chantal,Picard, Claude,Cazaux, Louis,Tisnes, Pierre
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p. 9793 - 9804
(2007/10/03)
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- Synthesis of Small-Medium Ring Thioanhydrides
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Reaction of five-membered ring anhydrides with sodium sulfide has previously been employed for synthesis of the corresponding thioanhydrides in low yields.Re-examination of the stoichiometry reveals reaction of cyclic anhydride with sodium sulfide (2:1 respectively), affords the thioanhydride accompanied by the corresponding dicarboxylate in a 1:1 molar ratio.The mechanistic pathway for this reaction has also been elucidated.Optimization of reaction conditions has resulted in the synthesis of a variety of four to seven-membered ring thioanhydride in yields approaching theoretical.
- Kates, Michael J.,Schauble, J. Herman
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p. 971 - 978
(2007/10/02)
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