- Butylphthalide ring-opening compound, pharmaceutical compound, and preparation methods, compositions and applications of butylphthalide ring-opening compound and pharmaceutical compound
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The invention relates to the field of medicines, and in particular, relates to a butylphthalide ring-opening compound, a pharmaceutical compound and preparation methods and applications of the butylphthalide ring-opening compound and the pharmaceutical compound. The butylphthalide ring-opening compound has a structure represented by a formula (I), wherein R1 and R2 are the same or different and are independently selected from H, C1-C5 alkyl, C1-C5 hetero-alkyl and -SO2R6, and R6 is selected from H, C1-C5 alkyl, C1-C5 hetero-alkyl, an aromatic ring and a heterocyclic ring from a three-membered ring to an eight-membered ring; or R1 and R2 are connected to form a three-membered ring to an eight-membered ring; and X is C or N or is absent to form a five-membered ring or a six-membered ring. The compound can be fully absorbed by the human body by being combined with an active substance, and the biological activity of the active substance is further promoted. Particularly, after the compound is combined with edaravone, a compound with excellent biological activity can be obtained.
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- Prodrug based on butylphthalide structure or pharmaceutically acceptable metal salt thereof as well as preparation method and application thereof
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The invention discloses a prodrug based on a butylphthalide structure or a pharmaceutically acceptable metal salt thereof, wherein the structural general formula I is shown in the specification; the prodrug can stably target a gastrointestinal monocarboxy
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Paragraph 0018; 0041-0043
(2021/04/21)
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- Novel brain-targeting 3-n-butylphthalide prodrugs for ischemic stroke treatment
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Currently, ischemic stroke is the leading cause of disability and death worldwide, and the performance of corresponding drugs is often unsatisfactory owing to the complex pathological processes and the impediment of the blood-brain barrier (BBB). Here, we
- Xiang, Honglin,Zhang, Qiang,Han, Yikun,Yang, Lan,Zhang, Yan,Liu, Qiang,Zhang, Zhirong,Zhang, Ling
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p. 498 - 514
(2021/06/11)
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- Butylphthalide ring-opening derivative as well as preparation method and application thereof
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The invention relates to a butylphthalide ring-opening derivative and a preparation method and application thereof. The butylphthalide ring-opening derivative can significantly improve the ischemia symptom of the cerebral ischemia reperfusion model rat, a
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Paragraph 0119-0123
(2021/09/21)
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- Design and synthesis of the ring-opened derivative of 3-n-butylphthalide-ferulic acid-glucose trihybrids as potential anti-ischemic agents
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To improve aqueous solubility and anti-ischemic activity of 3-n-butylphthalide (NBP), we designed and synthesized the ring-opened derivative of NBP-ferulic acid-glucose trihybrids (S1-S8). These hybrids inhibited adenosine diphosphate (ADP)- or arachidonic acid (AA)-induced platelet aggregation, among them, S2 was 30-fold more water-soluble, and over 10-fold more potent in inhibition of platelet aggregation, as well as reduced ROS generation and protected primary neuronal cells from OGD/R-induced damage, in comparison with NBP. Additionally, S2 was more active than its three moieties alone or in combination, suggesting that the activity of S2 may be attributed to the synergistic effects of these moieties. Importantly, in vivo studies indicated that S2 not only possessed good pharmacokinetic profile, but also improved NBP distribution in rodent brain, suggesting that the glucose moiety in S2 may be recognized by glucose transporter 1 (GLUT1) on blood-brain barrier (BBB), promoting it to penetrate through BBB. Our findings suggest that S2 may be a promising candidate for the intervention of ischemic stroke, warranting further study.
- Wu, Jianbing,Yin, Wei,Zhang, Yinqiu,Ye, Hui,Li, Yunman,Tian, Jide,Huang, Zhangjian,Zhang, Yihua
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p. 1881 - 1886
(2020/03/13)
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- Method for synthesizing 3 - n -butyl - l (3H)-isobenzofuranone (by machine translation)
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The invention discloses a method for synthesizing 3 - n -butyl - l (3H)-isobenzofuranone, firstly mixing Grignard reagent with Lewis acid, adjusting pH to acidity by an acid reagent, extracting with an organic solvent, concentrating and removing an organic solvent to obtain 3 - n -butyl - l (3H)-isobenzofuranone. (by machine translation)
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Paragraph 0060-0062
(2020/07/24)
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- Method for preparing high-purity butyphthalide
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The invention relates to a method for preparing high-purity butyphthalide. The method comprises the following steps: dissolving phthalaldehydic acid in an organic solvent, reacting with n-butyllithiumin a micro-channel reactor to generate a butyphthalide crude product, and carrying out aftertreatment to obtain the high-purity butyphthalide. The method overcomes the disadvantages that the yield for preparing the butyphthalide is low, the reaction temperature is high and the product color grade is high in existing phthalic acid method and valeric anhydride reaction; and moreover, the technicalproblems that magnesium ions are difficult to remove through aftertreatment and the high-purity butyphthalide is difficult for industrial production when the butyphthalide is prepared in the reactionof o-formoxyl benzoic acid and butyl magnesium bromide. The method is high in yield, the raw materials are easily obtained, and the prepared butyphthalide is high in purity and is applicable for industrial production.
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Paragraph 0052-0053; 0056-0057; 0060-0061
(2019/07/29)
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- BUTYLPHTHALIDE-TELMISARTAN HETEROCOMPLEX, PREPARATION METHOD AND APPLICATION THEREOF
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The invention discloses a butylphthalide-telmisartan heterocomplex, a preparation method and an application thereof. The invention specifically relates to an optically active ring-opening butylphthalide-telmisartan heterocomplex shown in formula I or a ph
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Paragraph 0092
(2019/12/30)
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- Simple method for preparing high-purify butyphthalide
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The invention provides a simple method for preparing high-purity butyphthalide. The simple method includes subjecting carboxybenzaldehyde, as a starting material, and normal-butyl halogenated (brominated or chlorinated) Grignard reagent or n-butyllithium to reaction in organic solution to obtain a reaction solution; after the reaction, adding water solution into the reaction solution dropwisely, extracting or removing organic solvents by reduction vaporization to obtain 2-(1-hydroxy-amyl) benzoate solution, subjecting 2-(1-hydroxy-amyl) benzoate solution to extraction by organic solvents whileregulating the pH to obtain 2-(1-hydroxy-amyl) benzoic acid, dissolving 2-(1-hydroxy-amyl) benzoic acid in organic solvents, performing cyclization reaction, sequentially washing with saturated sodium bicarbonate solution and sodium chloride solution, drying, and then performing reduced-pressure distillation to obtain high-purity butyphthalide. The synthesis method is simple and convenient to operate as column chromatography, reduced-pressure rectification or frequent acidifying or alkalizing or frequent to purify samples by ring-opening or ring-closing reactions are omitted, and accordinglyis adaptable to industrialized production. By the simple method, colorless products with purity being or higher than 99% can be obtained without decoloration or purification.
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Paragraph 0021
(2019/01/14)
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- Organic amine ester derivative drug of 2-(alpha hydroxyl amyl) benzoic acid
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The invention discloses a preparation method and an application of an organic amine derivative drug of 2-(alpha hydroxyl amyl) benzoic acid, and particularly relates to a compound shown as general formula I as shown in the specification, or pharmaceutical
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Paragraph 0028; 0029
(2018/11/22)
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- Ligustrazine-butyphthalide combination compound, preparation method of ligustrazine-butyphthalide combination compound, and application of ligustrazine-butyphthalide combination compound to pharmaceuticals
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The invention discloses a ligustrazine-butyphthalide combination compound, a preparation method of the ligustrazine-butyphthalide combination compound and an application of the ligustrazine-butyphthalide combination compound to pharmaceuticals. The ligustrazine-butyphthalide combination compound has the following structural formula I as in the description. The phthalic anhydride and the ligustrazine are taken as starting materials, bromization, nucleophilic addition, catalytic dehydration, ester hydrolysis, reduction and esterification reactions are conduced to prepare the ligustrazine-butyphthalide combination compound; a pharmaceutical composition takes the ligustrazine-butyphthalide combination compound as an active pharmaceutical ingredient and is a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, intermedium or a composition. The prepared ligustrazine-butyphthalide combination compound has an excellent effect of inhibiting in-vitro platelet aggregation (ADP) induced platelet aggregation, has a better in-vivo pharmacokinetics properties, and can be used for preventing and treating cardiovascular and cerebrovascular diseases, vascular senile dementia and the complications.
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- Butyphthalide preparation method
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The invention provides a butyphthalide preparation method which comprises the following steps: S1) utilizing raney nickel as a catalyst, performing hydrogenation reaction on butylidene phthalide in an alcohol solvent and reducing pressure to remove the solvent to obtain a first intermediate; S2) mixing the first intermediate, sodium hydroxide and water to react, then utilizing dichloromethane to wash a reaction system, then adding the alcohol solvent and performing acid adjusting reaction to obtain a second intermediate; S3) performing cyclization reaction on the second intermediate in an acid organic solvent to obtain butyphthalide. Compared with the prior art, the butyphthalide preparation method disclosed by the invention utilizes the alcohol solvent and the dichloromethane as reaction or extraction solvents; the alcohol solvent and the dichloromethane both can be effectively recycled and is low in cost, so that production cost is greatly reduced; through hydrolyzing purification and acid adjusting filtration purification, high-purity butyphthalide meeting a preparation requirement can be obtained in higher yield; the steps of reducing pressure and rectifying are avoided, and operation is simple.
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- Butylphthalide synthesis method and purification technology
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The invention relates to a butylphthalide synthesis method. The method comprises the steps that methyl 2-formyl benzoic acid is adopted as a starting material, THF is adopted as a solvent to react with an n-butyl magnesium chloride Grignard reagent, and acid regulation is performed to prepare a butylphthalide product. The invention further relates to a technology for preparing high-purity butylphthalide. The obtained crude butylphthalide product is subjected to hydrolysis treatment by an alkaline substance, acid regulation is performed to separate out solids, and filtering is performed to obtain a butylphthalide midbody; the acid regulation and alkali regulation processes are executed repeatedly, and finally ring closure and decompression desolvation are performed to obtain high-purity butylphthalide. According to the synthesis method, low-flash diethyl ether is prevented from being adopted as a solvent, the purification technology is easy to implement, the reagent can be purchased in bulk easily, column chromatography product purification and reduced pressure distillation under high temperature and high vacuum degree are not needed, and industrial enlarged production is easy.
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Paragraph 0065; 0066; 0067-0071
(2017/05/26)
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- Novel hybrids of 3-n-butylphthalide and edaravone: Design, synthesis and evaluations as potential anti-ischemic stroke agents
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Abstract Fourteen hybrids (10a-g, 11a-g) of 3-n-butylphthalide (NBP) and edaravone (Eda) analogues have been designed and synthesized as potential anti-ischemic stroke agents. In vitro biological studies showed that compounds 10d and 10g exhibited more potent anti-platelet aggregation than ticlopidine (Ticlid), aspirin (ASP) and NBP. Compound 10g more significantly prevented H2O2-mediated neuronal cell (PC12) death than NBP, Eda or NBP together with Eda. Meanwhile, 10g also possessed potent radical scavenging effects on hydroxyl radical (·OH) and superoxide anion radical (·O2-). Our findings may provide new insights into the development of these hybrids, like 10g, for the intervention of ischemic stroke.
- Sheng, Xiao,Hua, Kai,Yang, Chunyu,Wang, Xiaoli,Ji, Hui,Xu, Jinyi,Huang, Zhangjian,Zhang, Yihua
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p. 3535 - 3540
(2015/08/06)
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- Design, synthesis and biological evaluation of hydrogen sulfide releasing derivatives of 3-n-butylphthalide as potential antiplatelet and antithrombotic agents
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In the present study, a series of hydrogen sulfide (H2S) releasing derivatives (8a-g and 9a-f) of 3-n-butylphthalide (NBP) were designed, synthesized and biologically evaluated. The most promising compound 8e significantly inhibited the adenosi
- Wang, Xiaoli,Wang, Linna,Sheng, Xiao,Huang, Zhangjian,Li, Tingting,Zhang, Ming,Xu, Jinyi,Ji, Hui,Yin, Jian,Zhang, Yihua
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p. 5995 - 6004
(2014/08/05)
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- Studies on the enantiomers of ZJM-289: Synthesis and biological evaluation of antiplatelet, antithrombotic and neuroprotective activities
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ZJM-289 is a potent racemic agent which inhibits both platelet aggregation and thrombosis superior to a known anti-ischemic stroke drug 3-n-butylphthalide (NBP). Herein, the enantiomers of ZJM-289, (S)-ZJM-289 and (R)-ZJM-289, were synthesized and evaluat
- Wang, Xiaoli,Zhao, Qian,Wang, Xuliang,Li, Tingting,Lai, Yisheng,Peng, Sixun,Ji, Hui,Xu, Jinyi,Zhang, Yihua
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p. 9030 - 9040
(2013/01/15)
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- Design, synthesis and evaluation of nitric oxide releasing derivatives of 3-n-butylphthalide as antiplatelet and antithrombotic agents
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Novel nitric oxide (NO) releasing derivatives (7a-7l) of 3-n-butylphthalide (NBP) were designed and synthesized. Compound 7e inhibited the adenosine diphosphate (ADP), thrombin (TH) and arachidonic acid (AA)-induced in vitro platelet aggregation, superior to NBP and aspirin, released moderate levels of NO, and improved aqueous solubility relative to NBP. Furthermore, 7e exhibited greater antithrombotic activity than NBP and aspirin in rats, and protected against collagen and adrenaline-induced thrombosis in mice. Therefore, NO-releasing NBP derivatives possessed potent antiplatelet aggregation and antithrombotic activity. Our findings may aid in the design of new therapeutic agents for the treatment of thrombosis-related ischemic stroke.
- Wang, Xuliang,Li, Yang,Zhao, Qian,Min, Zhenli,Zhang, Chao,Lai, Yisheng,Ji, Hui,Peng, Sixun,Zhang, Yihua
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p. 5670 - 5681
(2011/09/15)
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- Synthesis and evaluation of nitric oxide-releasing derivatives of 3-n-butylphthalide as anti-platelet agents
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Most ischemic stroke results from brain blood vessel blockage by platelet-mediated thrombus, and anti-platelet therapy has been demonstrated clinical benefits in the treatment of this disease. In the present work, novel nitric oxide (NO)-releasing derivatives of an anti-ischemic stroke drug 3-n-butylphthalide (NBP) were synthesized. Compounds 7a and 7c exhibited more potent anti-platelet activity than NBP and aspirin, and released a moderate amount of NO, which is beneficial in improving cardiovascular and cerebral circulation. These findings provide an alternative approach to the development of drugs more potent than NBP for the intervention of ischemic stroke.
- Li, Yang,Wang, Xuliang,Fu, Rong,Yu, Wenying,Wang, Xiaoli,Lai, Yisheng,Peng, Sixun,Zhang, Yihua
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scheme or table
p. 4210 - 4214
(2011/08/06)
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