- Novel ligustrazine derivative as well as preparation method and application thereof
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The invention provides a novel ligustrazine derivative as well as a preparation method and application thereof. Experiments prove that the ligustrazine derivative can effectively protect nerve cells and myocardial cells from CoCl2 hypoxia injury; and meanwhile, the ligustrazine derivative has the effect of remarkably inhibiting platelet aggregation. Therefore, the ligustrazine derivative disclosed by the invention can be used for preparing medicines for effectively preventing or treating central nervous system diseases and/or thrombotic diseases; more importantly, the effect of the ligustrazine derivative is obviously superior to that of ligustrazine with the same dosage. The invention widens the new application of the novel ligustrazine derivative, and has huge economic and social values.
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- Ligustrazine derivative and preparation method and medical application thereof
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The invention discloses a ligustrazine derivative and a preparation method and medical application thereof. The invention synthesizes and prepares three ligustrazine derivatives with novel structures,and provides a preparation method of the ligustrazine derivatives. Pharmacological results show that the inhibitory activity of the three ligustrazine derivatives I-2, I-4 and I-6 on ADP-induced or AA-induced platelet aggregation is superior to that of a parent compound ligustrazine (TMP); compared with clinically common medicines with anticoagulant effects, the activity of the ligustrazine derivatives I-2, I-4 and I-6 in inhibition of ADP-induced platelet aggregation is equivalent to that of a positive drug thilopyrazine, and the inhibition activity of the ligustrazine derivatives I-2, I-4 and I-6 in inhibition of AA-induced platelet aggregation is obviously superior to that of a positive control drug aspirin.
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- Pyrazine compound and preparation method thereof
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The invention relates to a pyrazine compound, a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof, wherein the pyrazine compound, the stereoisomer, the tautomer and the pharmaceutically acceptable salt thereof can treat Alzheimer's disease, Parkinson's disease, Huntington's disease, frontal temporal dementia (FTD), vascular dementia, HIV-related dementia, multiple sclerosis,progressive spinal cord lateral sclerosis, Friedel-Crafts ataxia, neuropathic pain or glaucoma and other neurodegenerative diseases, diabetes mellitus and related diabetic complications, inflammations, oxidative damage and mitochondria-related diseases.
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Paragraph 0060-0062
(2020/11/09)
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- Application of pyrazine compound in preparation of drugs
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The invention relates to an application of a pyrazine compound in preparation of drugs. The drugs can be used for treating neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal dementia (FTD), vascular dementia, HIV-related dementia, multiple sclerosis, progressive lateral sclerosis, Friedreich's ataxia, neuropathic pain or glaucoma, inflammation, oxidative damage, and mitochondrial-related diseases.
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Paragraph 0063-0065
(2020/10/30)
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- Discovery of a new tetramethylpyrazine based chalcone with α, β-unsaturated ketone moiety as a potential anticancer agent
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In this study, a new ligustrazine-based chalcone molecule has been synthesized that contains an extra α, β-Unsaturated ketone moiety along with α, the β-Unsaturated carbonyl group of chalone. A new tetramethylpyrazine (TMP) based aldehyde was synthesized to make the TMP (ligustrazine) as part of chalcone and then it was reacted with newly synthesized ketone containing additional α, β-Unsaturated ketone moiety. After characterization, this new compound was evaluated for its effect on different types of cancer cell lines and very promising results were obtained. The growth of these cancer cells was inhibited by newly designed and synthesized compounds, especially for colon and pancreatic cancer cells with IC50 0.04-0.05 μM.
- Bukhari, Syed Nasir Abbas
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p. 826 - 829
(2020/02/25)
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- Ligustrazine derivative, and preparation method and applications thereof
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The invention provides a ligustrazine derivative, and a preparation method and applications thereof. The ligustrazine derivative is capable of treating IAA induced hypoxic injury, promoting neuron cell proliferation, promoting cell synapsis lengthening, and can be used for treating stroke and neurodegenerative diseases.
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- Reduction-sensitive nanomicelle and preparation method and application thereof
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The invention discloses a preparation method and application of a reduction-sensitive nanomicelle, belongs to the technical field of nanomedicine, and particularly provides a preparation method of anamphiphilic prodrug self-assembled nanomicelle of methylpyrazine combined with paclitaxel or docetaxel and application of the nanomicelle in anti-tumor research. Through a nanoprecipitation approach and a dialysis approach, disulfide-bonded ligustrazine and a methylpyrazine analog thereof and the paclitaxel or the docetaxel are adopted for preparing prodrugs which are self-assembled into the nanomicelle, the operation is easy and convenient to implement, the particle size is small and uniform, the drug loading amount is high, and the nanomicelle can respond to a tumor microreduction environment, so that the tumor selectivity of the paclitaxel is improved, the effect of targeted treatment of tumors is achieved, the enrichment of drug concentration at tumor sites is improved, and the nanomicelle achieves good synergism and toxicity reduction effects in in-vivo and in-vitro anti-tumor application.
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- Ligustrazine/azoonium diol salt derivative as well as preparation method and application thereof
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The invention discloses a ligustrazine/azoonium diol salt derivative as well as a preparation method and application thereof. The derivative has a structure as shown in a formula (I) which is described in the specification, wherein R1 and R2 are the same or different; the R1 and R2 are the same or different and independently represent a hydrogen atom and a C1-C4 alkyl group, and the R1 and R2 forma 5- to 7-membered aliphatic heterocyclic ring or aromatic heterocyclic ring along with the nitrogen atom to which R1 and R2 are connected.; the aliphatic heterocycle or the aromatic heterocycle maybe optionally mono-substituted to penta-substituted by the same or different substituents, the substituents being a C1-C6 alkyl group, a C1-C6 alkoxy group, a hydroxyl group, or a halogen. The ligustrazine/azoonium diol salt derivative provided by the invention can inhibit proliferation of tumor cells to different extents. Besides, compared with common breast cancer cells, the ligustrazine/azoonium diol salt derivative provided by the invention has a stronger proliferation inhibition effect on drug-resistant breast cancer cells, and prompts that the ligustrazine/azoonium diol salt derivative has a good application prospect on drug-resistant tumors.
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- BA-12 inhibits angiogenesis via glutathione metabolism activation
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There is a need for an efficient and low-cost leading compound discovery mode. However, drug development remains slow, expensive, and risky. Here, this manuscript proposes a leading compound discovery strategy based on a combination of traditional Chinese medicine (TCM) formulae and pharmacochemistry, using a ligustrazine-betulinic acid derivative (BA-12) in the treatment of angiogenesis as an example. Blocking angiogenesis to inhibit the growth and metastasis of solid tumors is currently one recognized therapy for cancer in the clinic. Firstly, based on a traditional Prunella vulgaris plaster, BA-12 was synthesized according to our previous study, as it exhibited better antitumor activities than other derivatives on human bladder carcinoma cells (T24); it was then uploaded for target prediction. Secondly, the efficacy and biotoxicity of BA-12 on angiogenesis were evaluated using human umbilical vein endothelial cells (HUVECs), a quail chick chorioallantoic membrane, and Caenorhabditis elegans. According to the prediction results, the main mechanisms of BA-12 were metabolic pathways. Thus, multiple metabolomics approaches were applied to reveal the mechanisms of BA-12. Finally, the predictive mechanisms of BA-12 on glutathione metabolism and glycerophospholipid metabolism activation were validated using targeted metabolomics and pharmacological assays. This strategy may provide a reference for highly efficient drug discovery, with the aim of sharing TCM wisdom for unmet clinical needs.
- Cui, Herong,Guo, Wenbo,Zhang, Beibei,Li, Guoping,Li, Tong,Yuan, Yanyan,Zhang, Na,Yang, Yuwei,Feng, Wuwen,Chu, Fuhao,Wang, Shenglan,Xu, Bing,Wang, Penglong,Lei, Haimin
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- Novel homo-bivalent and polyvalent compounds based on ligustrazine and heterocyclic ring as anticancer agents
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Bivalent and polyvalent inhibitors can be used as antitumor agents. In this experiment, eight ligustrazine dimers and seven ligustrazine tetramers linked by alkane diamine with different lengths of carbon chain lengths were synthesized. After screening their antiproliferation activities against five cancer cell lines, most ligustrazine derivatives showed better cytotoxicity than the ligustrazine monomer. In particular, ligustrazine dimer 8e linked with decane-1,10-diamine exhibited the highest cytotoxicity in FaDu cells with an IC50 (50% inhibiting concentration) value of 1.36 nM. Further mechanism studies suggested that 8e could induce apoptosis of FaDu cells through the depolarization of mitochondrial membrane potential and S-phase cell cycle arrest. Inspired by these results, twenty-seven additional small molecule heterocyclic dimers linked with decane-1,10-diamine and nine cinnamic acid dimers bearing ether chain were synthesized and screened. Most monocyclic and bicyclic aromatic systems showed highly selective anti-proliferation activity to FaDu cells and low toxicity to normal MCF 10A cells. The structure-activity relationship revealed that the two terminal amide bonds and the alkyl linker with a chain length of 8–12 carbon were two important factors to maintain its antitumor activity. In addition, the ADMET calculation predicted that most of the potent compounds had good oral bioavailability.
- Wang, Jiawen,Hong, Ge,Li, Guoliang,Wang, Wenzhi,Liu, Tianjun
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- TRIFLUOROACETYL HYDRAZIDE COMPOUNDS AND MEDICAL USES THEREOF
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The present invention relates to trifluoroacetyl hydrazide compounds and medical uses thereof. The compounds have a structure of the following formula: The compounds showed multifunctional mechanisms, including inhibition of glutamate excitotoxicity, activation of MEF2 transcriptional activity, clearance of free radicals, and promotion of nerve differentiation, and has a better protective effect on cells especially nerve cells. The compound can be used to prepare prophylactic or therapeutic medicaments with cytoprotective effects, for the prevention or treatment of diseases related to glutamate receptor activation, MEF2 disorders or excessive free radicals generation. The diseases include, for example, neurodegenerative diseases such as Alzheimer's disease, Parkinson and stroke, and the free radicals related diseases such as heart disease, myocardial ischemia, diabetes and other cardiovascular and cerebrovascular diseases.
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Paragraph 0038
(2019/07/29)
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- Chloroxime compound as well as preparation method and application thereof in pharmacy
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The invention relates to a chloroxime compound, its preparation method and application in pharmacy. The chloroxime compound has a structure shown as the general formula I in the specification. The compounds has a very strong effect in synergistic regulation of heat shock protein activity, can be used for treating neurodegenerative diseases caused by injection of Abeta1-42 to rats, and aims to treat human neurodegenerative diseases. The compound also has a significant stress resistant effect, and can be used for preparation of new drugs treating diseases caused by protein misfolding and/or aggregation, and oxidative stress.
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- Novel Ligustrazine-Based Analogs of Piperlongumine Potently Suppress Proliferation and Metastasis of Colorectal Cancer Cells in Vitro and in Vivo
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Piperlongumine 1 increases reactive oxygen species (ROS) levels and preferably induces cancer cell apoptosis by triggering different pathways. However, the poor solubility of 1 limits its intensive investigation and clinical application. Ligustrazine possesses a water-soluble pyrazine skeleton and can inhibit proliferation and metastasis of cancer cells. We synthesized compound 3 by replacement of the trimethoxyphenyl of 1 with ligustrazine moiety and further introduced 2-Cl, -Br, and -I to 3 for synthesis of 4-6, respectively. Compound 4 possessed 14-fold greater aqueous solubility than 1 and increased ROS levels in colorectal cancer HCT-116 cells. Additionally, 4 preferably inhibited proliferation, migration, invasion, and heteroadhesion of HCT-116 cells. Treatment with 4 suppressed tumor growth and lung metastasis in vivo and prolonged the survival of tumor-bearing mice. Furthermore, 4 mitigated TGF-β1-induced epithelial-mesenchymal transition and Wnt/β-catenin activation by inhibiting the Akt and GSK-3β phosphorylation in HCT-116 cells. Collectively, 4 displayed significant antiproliferation and antimetastasis activities, superior to 1.
- Zou, Yu,Zhao, Di,Yan, Chang,Ji, Yanpeng,Liu, Jin,Xu, Jinyi,Lai, Yisheng,Tian, Jide,Zhang, Yihua,Huang, Zhangjian
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p. 1821 - 1832
(2018/03/21)
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- Antitumor compound and preparation method thereof
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Belonging to the technical field of medicine, the invention discloses an antitumor compound and a preparation method thereof, and specifically provides a conjugate of methylpyrazine and paclitaxel ordocetaxel. A disulfide bond is adopted as the connecting bridge for chemical bonding of ligustrazine and its analogue methylpyrazine with paclitaxel or docetaxel. Construction of the amphiphilic compound can improve the water solubility of paclitaxel and docetaxel so as to improve the bioavailability; the active targeting of the disulfide bond can enhance the selectivity of paclitaxel and docetaxel, thereby reducing the lethality to healthy cells and normal tissues; after release of the conjugate when it reaches a target site, ligustrazine can assist paclitaxel and docetaxel in playing an antitumor role together, while the drug resistance is improved, the antitumor effect is enhanced.
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- Ligustrazine chalcone compound and preparation method and application thereof
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The invention relates to a ligustrazine chalcone compound and a preparation method and application thereof. The ligustrazine chalcone compound is an antioxidant with a series of novel structure, and better antioxidation activities are shown by most of compounds, so that the ligustrazine chalcone compound has further studying and developing value, and the ligustrazine chalcone compound can be usedas a lead compound of the antioxidant. The invention further provides the application of preparing antioxidation medicines of the compound and a composition containing one or more compounds.
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- Compound BA-X having antitumor effect, preparation method and applications thereof
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The present invention provides a class of compounds having a structure represented by a general formula 1, and a preparation method thereof, and applications in preparation of antitumor drugs. According to the present invention, the compound can significantly inhibit the growth of tumor cell lines (HepG-2, HT-29, Hela, BGC-823 and A549) while has low toxicity on Madin-Darby canine kidney (MDCK) cells, wherein the compound BH-26 has good anti-proliferative activity against colonic carcinoma cell line HT-29, human cervical cancer cell line Hela and human gastric cancer cell line BGC823 comparedto the positive drug cisplatin, and has significantly low cytotoxicity to normal Madin-Darby canine kidney (MDCK) cells compared to the positive drug cisplatin. The formula 1 is defined in the specification.
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- Synthesis and biological evaluation of new tetramethylpyrazine-based chalcone derivatives as potential anti-Alzheimer agents
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In the current study, a series of new ligustrazine-based chalcones was synthesized. For insertion of tetramethylpyrazine (TMP, also designated as ligustrazine) in chemical backbone of chalcone, a new ligustrazine-based aldehyde was prepared. New ketones were synthesized for inclusion of quinazolin-4-yl amino and pyrazin-2-yl amino moieties. The newly synthesized compounds were screened for acetylcholinesterase, butyrylcholinesterase, and monoamine oxidases (MAO) inhibitory activities and also for in vitro cytotoxicity on PC12 cells. The effect of these compounds against amyloid β-induced cytotoxicity and aggregation was also investigated. The synthesized compounds effectively inhibited the related enzymes and also exhibited neuroprotective effects. Most of the compounds displayed better inhibitory potencies against Aβ aggregation than reference compounds. Some compounds such as 11e and 16b showed very potent effects on multiple targets exhibiting behavior as multifunctional anti-Alzheimer agents.
- Wang, Meng,Qin, Hua-Li,Leng, Jing,Ameeduzzafar,Amjad, Muhammad Wahab,Raja, Maria Abdul Ghafoor,Hussain, Muhammad Ajaz,Bukhari, Syed Nasir Abbas
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p. 1859 - 1866
(2018/07/31)
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- Synthesis and evaluation of novel ligustrazine derivatives as multi-targeted inhibitors for the treatment of Alzheimer's disease
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A series of novel ligustrazine derivatives 8a-r were designed, synthesized, and evaluated as multi-targeted inhibitors for anti-Alzheimer's disease (AD) drug discovery. The results showed that most of them exhibited a potent ability to inhibit both ChEs, with a high selectivity towards AChE. In particular, compounds 8q and 8r had the greatest inhibitory abilities for AChE, with IC50 values of 1.39 and 0.25 nM, respectively, and the highest selectivity towards AChE (for 8q, IC50BuChE/IC50 AChE = 2.91 × 106; for 8r, IC50BuChE/IC50 AChE = 1.32 × 107). Of note, 8q and 8r also presented potent inhibitory activities against Aβ aggregation, with IC50 values of 17.36 μM and 49.14 μM, respectively. Further cellular experiments demonstrated that the potent compounds 8q and 8r had no obvious cytotoxicity in either HepG2 cells or SH-SY5Y cells, even at a high concentration of 500 μM. Besides, a combined Lineweaver-Burk plot and molecular docking study revealed that these compounds might act as mixed-type inhibitors to exhibit such effects via selectively targeting both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChEs. Taken together, these results suggested that further development of these compounds should be of great interest.
- Wu, Wenhao,Liang, Xintong,Xie, Guoquan,Chen, Langdi,Liu, Weixiong,Luo, Guolin,Zhang, Peiquan,Yu, Lihong,Zheng, Xuehua,Ji, Hong,Zhang, Chao,Yi, Wei
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- Compound TVA-X having neuroprotection effect, preparation method and applications thereof
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The invention relates to a compound TVA-X having neuroprotection effect, a preparation method and applications thereof, and provides a class of compounds having a structure general formula 1, and a preparation method thereof, and applications in preparation of drugs for treatment of brain nerve injury and sequela thereof, wherein the composition can significantly protect cobalt chloride induced PC12 cell damage, wherein the compound VA-06 has strong protection effect on cobalt chloride induced PC12 cell damage compared to the positive drug ligustrazine. The formula 1 is defined in the specification.
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Paragraph 0068; 0069
(2018/09/14)
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- TRIFLUOROACETYL HYDRAZIDE COMPOUNDS AND METHODS OF PREPARATION AND USES THEREOF
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The present invention relates to trifluoroacetyl hydrazide compounds and methods of preparation and uses thereof. The compounds have a structure of the following formula: The compounds showed multifunctional mechanisms, including inhibition of glutamate excitotoxicity, activation of MEF2 transcriptional activity, clearance of free radicals, and promotion of nerve differentiation, and has a better protective effect on cells especially nerve cells. The compound can be used to prepare prophylactic or therapeutic medicaments with cytoprotective effects, for the prevention or treatment of diseases related to glutamate receptor activation, MEF2 disorders or excessive free radicals generation. The diseases include, for example, neurodegenerative diseases such as Alzheimer's disease, Parkinson and stroke, and the free radicals related diseases such as heart disease, myocardial ischemia, diabetes and other cardiovascular and cerebrovascular diseases.
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Paragraph 0038
(2019/01/04)
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- Combination of amino acid/dipeptide with ligustrazine-betulinic acid as antitumor agents
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The lead compound TBA, 3β-Hydroxy-lup-20(29)-ene-28-oic acid-3, 5, 6-trimethylpyrazin-2-methyl ester, which exhibited promising antitumor activity and induced tumor cell apoptosis in various cancer cell lines, had previously been reported. Moreover, reports have revealed that the introduction of amino acid to betulinic acid could improve selective cytotoxicity as well as water solubility. Thus, a series of novel TBA amino acid and dipeptide derivatives were designed, synthesized and screened for selective cytotoxic activity against five cancer cell lines (HepG2, HT-29, Hela, BCG-823 and A549) and the not malignant cell line MDCK by standard MTT assay. Most of the tested TBA-amino acid and dipeptide analogues showed stronger anti-proliferative activity against all tested tumor cell lines than TBA. Among them, BA-25 exhibited the greatest cytotoxic activity on tumor cell lines (mean IC50= 2.31 ± 0.78 μM), that was twofold than the positive drug cisplatin (DDP), while it showed lower cytotoxicity on MDCK cell line than DDP. Further cell apoptosis analyses indicated BA-25-induced apoptosis was associated with loss of mitochondrial membrane potential and increase of intracellular free Ca2+concentration.
- Xu, Bing,Yan, Wen-Qiang,Xu, Xin,Wu, Gao-Rong,Zhang, Chen-Ze,Han, Yao-Tian,Chu, Fu-Hao,Zhao, Rui,Wang, Peng-Long,Lei, Hai-Min
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- Design, synthesis and evaluation of new ligustrazine derivatives as potential plasma-stable neuroprotective agents
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A series of ligustrazine-phenolic acid esters which exhibited promising neuroprotective activities have previously been reported. Nevertheless, we found that these ester compounds (like T-VA) were not stable in plasma by further in vivo studies. To investigate plasma-stable neuroprotective agents, a series of new ligustrazine derivatives were synthesized by conjoining ligustrazine and phenols with ester, ether and amide bonds. Most of the compounds exhibited higher protective effects against CoCl2-induced neurotoxicity in differentiated PC12 cells than ligustrazine. Structure-activity relationships were also briefly discussed. We found that compound 2c (2-((2-methoxy-4-(((3,5,6-trimethylpyrazin-2-yl)methoxy) methyl)phenoxy)methyl)-3,5,6-trimethylpyrazine) displayed the highest protective effect on the PC12 cells damaged by CoCl2 (EC50 = 1.07 μM). Preliminary stability investigation in rat plasma was verified in vitro and better plasma stability was observed with 2c in comparison to T-VA.
- Zhang, Chenze,Yan, Wenqiang,Zhao, Rui,Xu, Bing,Fang, Xiong,Yan, Mengmeng,Zhang, Yuzhong,Wang, Penglong,Lei, Haimin
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p. 652 - 656
(2017/03/30)
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- A kind of Rhizoma Chuanxiong oxadiazine derivatives, preparation method and application thereof (by machine translation)
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The invention relates to the field of pharmaceutical chemistry, and in particular relates to a kind of Rhizoma Chuanxiong oxadiazine derivatives (I) and (II) and its preparation method, the pharmacodynamics tests prove that, Rhizoma Chuanxiong oxadiazine derivatives of this invention has a certain anti-tumor activity and significant inhibition of tumor cell migration and attack role, can be used for the treatment of tumor. (by machine translation)
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- Synthesis and biological evaluation of ligustrazine derivatives
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Synthesized ligustrazine derivatives (1a, 1b, 1c (novel)) were structurally confirmed by mass spectrometry,1H NMR, and 13C NMR. The cytotoxic activities of all derivatives were evaluated by MTS assay in three human prostate cancer cell lines (PC-3, LNCaP, and DU145) and in the A549 human lung cancer cell line. Compound 1a exhibited strong cytotoxic activity against PC-3 cells (IC50 3.63μM). In addition, compounds 1-1c showed moderate α1-adrenergic receptor (AR) subselective antagonistic and β2-AR agonistic effects, indicating potential use for the treatment of chronic obstructive pulmonary disease. Molecular docking results showed 1b bound to one region of the active site in β2-AR, but 1, 1a, and 1c bound to a different region.
- Zhang, Chao,Chen, Lang-Di,Liang, Xin-Tong,Liu, Wei-Xiong,Wu, Wen-Hao
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p. 114 - 117
(2017/09/30)
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- A method for the preparation of benzimidazole derivatives
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The invention belongs to the technical field of compound preparation method, and specifically relates to a preparation method of a pharmaceutical compound used for hypertension treatment. The pharmaceutical compound is a benzimidazole derivative, and specifically is a substituted compound obtained via esterification of azilsartan; and the structural formula of the benzimidazole derivative is represented by formula 6 in the patent specification. It is confirmed by drug effect experiment results that bioavailability and activity of the benzimidazole derivative are both higher than that of azilsartan medoxomil. According to the preparation method, ligustrazine is taken as an initial raw material, is subjected to oxidation, rearrangement, hydrolysis, and acylation with 1-chloroethyl chloroformate, and is subjected to esterification with azilsartan in the presence of an alkali; and an obtained crude product is subjected to column chromatography and recrystallization; purity of an obtained product is determined to be higher than 99% via HPLC detection; and rearrangement product content is less than 0.5%. The scheme of the preparation method is reasonable; route is short; the raw materials are easily available; and the preparation method is suitable for amplification production.
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- Design, synthesis, and biological evaluation of novel tetramethylpyrazine derivatives as potential neuroprotective agents
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Oxidative stress plays a crucial role in neurological diseases, resulting in excessive production of reactive oxygen species, mitochondrial dysfunction and cell death. In this work, we designed and synthesized a series of tetramethylpyrazine (TMP) derivatives and investigated their abilities for scavenging free radicals and preventing against oxidative stress-induced neuronal damage in vitro. Among them, compound 22a, consisted of TMP, caffeic acid and a nitrone group, showed potent radical-scavenging activity. Compound 22a had broad neuroprotective effects, including rescuing iodoacetic acid-induced neuronal loss, preventing from tert-butylhydroperoxide (t-BHP)-induced neuronal injury. Compound 22a exerted its neuroprotective effect against t-BHP injury via activation of the phosphatidyl inositol 3-kinase (PI3K)/Akt signaling pathway. Furthermore, in a rat model of permanent middle cerebral artery occlusion, compound 22a significantly improved neurological deficits, and alleviated the infarct area and brain edema. In conclusion, our results suggest that compound 22a could be a potential neuroprotective agent for the treatment of neurological disease, particularly ischemic stroke.
- Chen, Haiyun,Tan, Guolian,Cao, Jie,Zhang, Gaoxiao,Yi, Peng,Yu, Pei,Sun, Yewei,Zhang, Zaijun,Wang, Yuqiang
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- Discovery of potential anticancer multi-targeted ligustrazine based cyclohexanone and oxime analogs overcoming the cancer multidrug resistance
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The drug research and development nowadays is focusing on multi-target drugs. In the treatment of cancer, therapies using drugs inhibiting one numerous targets signify a novel viewpoint. In comparison with traditional therapy, multi-targeted drugs directly aim cell subpopulations which are involved in progression of tumor. The current study comprises the synthesis of 34 novel ligustrazine-containing α, β-unsaturated carbonyl-based compounds and oximes. The growth of 5 various cancer cell types was strongly inhibited by ligustrazine-containing oximes as revealed by biological evaluation. A strong SAR was provided by the antiproliferative activity. The mechanistic effects of most active antiproliferative compounds on tubulin polymerization, EGFR TK kinases, KAF and BRAFV600E were investigated, followed by in?vitro investigation of reversal of efflux-based resistance developed by cancer cells. EGFR was strongly inhibited by two oximes 7e and 8o. Out of all linkers including positive control, 1-isopropyl-piperidin-4-one linker-bearing compounds showed best inhibition of FAK. The strongest inhibitory activity of BRAFV600E was showed by compound 5e with an IC50 of 0.7?μM. Analogs such as 5 and 7 (b,e,f) exhibited a dual role as anticancer as well as MDR reversal agents. For understanding the target protein integrations with new compounds, molecular docking studies were also carried out.
- Zha, Gao-Feng,Qin, Hua-Li,Youssif, Bahaa G.M.,Amjad, Muhammad Wahab,Raja, Maria Abdul Ghafoor,Abdelazeem, Ahmed H.,Bukhari, Syed Nasir Abbas
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- Compound containing ligustrazine chalcone aryloxy acids and preparing method and application of compound
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The invention relates to the field of medical chemistry, in particular to a compound (I) containing ligustrazine chalcone aryloxy acids and a preparing method of the compound. It is proved through pharmacodynamic tests that the compound has the medical application of treating hyperlipidemia and antherosclerosis. The formula is shown in the specification.
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- COMPOUNDS WITH NEURAL PROTECTIVE EFFECT, AND PREPARATION AND USE THEREOF
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The invention generally relates to compounds of formula (I) with neural protective effect, and preparation and uses thereof. The compounds have multiple mechanisms or functions, for example, inhibition of monoamine oxidase and cholinesterase, scavenging of free radicals, and protection of cells such as nerve cells. The compounds can be used for manufacture of medicaments of cell protection, for prevention and/or treatment of monoamine oxidase, cholinesterase and free radicals related diseases, for example, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and stroke, and free-radical related diseases such as heart disease, myocardial ischemia, diabetes and other cardiovascular and cerebrovascular diseases.
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Paragraph 0108
(2016/11/28)
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- Discovery of New Monocarbonyl Ligustrazine-Curcumin Hybrids for Intervention of Drug-Sensitive and Drug-Resistant Lung Cancer
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The elevation of oxidative stress preferentially in cancer cells by inhibiting thioredoxin reductase (TrxR) and/or enhancing reactive oxygen species (ROS) production has emerged as an effective strategy for selectively targeting cancer cells. In this study, we designed and synthesized 21 ligustrazine-curcumin hybrids (10a-u). Biological evaluation indicated that the most active compound 10d significantly inhibited the proliferation of drug-sensitive (A549, SPC-A-1, LTEP-G-2) and drug-resistant (A549/DDP) lung cancer cells but had little effect on nontumor lung epithelial-like cells (HBE). Furthermore, 10d suppressed the TrxR/Trx system and promoted intracellular ROS accumulation and cancer cell apoptosis. Additionally, 10d inhibited the NF-κB, AKT, and ERK signaling, P-gp-mediated efflux of rhodamine 123, P-gp ATPase activity, and P-gp expression in A549/DDP cells. Finally, 10d repressed the growth of implanted human drug-resistant lung cancer in mice. Together, 10d acts a novel TrxR inhibitor and may be a promising candidate for intervention of lung cancer.
- Ai, Yong,Zhu, Bin,Ren, Caiping,Kang, Fenghua,Li, Jinlong,Huang, Zhangjian,Lai, Yisheng,Peng, Sixun,Ding, Ke,Tian, Jide,Zhang, Yihua
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p. 1747 - 1760
(2016/03/25)
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- COMPOUNDS WITH NEURAL PROTECTIVE EFFECT, AND PREPARATION AND USE THEREOF
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The invention generally relates to compounds of formula (I) with neural protective effect, and preparation and uses thereof. The compounds have multiple mechanisms or functions, for example, inhibition of monoamine oxidase and cholinesterase, scavenging of free radicals, and protection of cells such as nerve cells. The compounds can be used for manufacture of medicaments of cell protection, for prevention and/or treatment of monoamine oxidase, cholinesterase and free radicals related diseases, for example, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and stroke, and free-radical related diseases such as heart disease, myocardial ischemia, diabetes and other cardiovascular and cerebrovascular diseases.
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Page/Page column 17; 18
(2015/08/06)
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- Ligustrazine derivatives. Part 8: Design, synthesis, and preliminary biological evaluation of novel ligustrazinyl amides as cardiovascular agents
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A series of novel Ligustrazinyl amides was designed, synthesized and evaluated for their protective effect onthe injured vascular endothelial cells. The preliminary results demonstrated that some compounds possessed more potentactivities than that of Ligustrazine in stimulating replication of the injured human umbilical vascular endothelial cells(HUVECs) that is damaged by hydrogen peroxide. Among the active compounds, compounds 8i, 8t and 8u exhibited thehighest potency with low EC50 values of 0.037, 0.070 and 0.055 mM, respectively. Structure-activity relationships werebriefly discussed.
- Li, Zhenyu,Yu, Fang,Cui, Lei,Chen, Wenmin,Wang, Shouxun,Zhan, Peng,Shen, Yuemao,Liu, Xinyong
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- Ligustrazine Derivatives. Part 4: Design, Synthesis, and Biological Evaluation of Novel Ligustrazine-based Stilbene Derivatives as Potential Cardiovascular Agents
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A series of novel stilbene derivatives containing ligustrazinyl moiety was designed, synthesized, and assayed for their protective effects on damaged endothelial cells. The results showed that most ligustrazinyl stilbene derivatives exhibited high protective effects on the human umbilical vascular endothelial cells (HUVECs) damaged by hydrogen peroxide in comparison with Ligustrazine. The stilbene derivatives A6, A9, A11, A21, A24, A25, and A27 exhibited high potency with low EC50 values ranged from 0.0249μm to 0.0898mm. Compound A27 displayed EC50 0.0249μm, which is 30000 times higher than that of Ligustrazine, presenting a most promising lead for further investigation. Structure-activity relationships were briefly discussed.
- Deng, Lijuan,Guo, Xiuli,Zhai, Li,Song, Yuning,Chen, Hongfei,Zhan, Peng,Wu, Jingde,Liu, Xinyong
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p. 731 - 739
(2012/05/20)
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- Ligustrazine derivatives. Part 6: Design, synthesis and evaluation of novel ligustrazinyl acylguanidine derivatives as potential cardiovascular agents
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A series of novel Ligustrazinyl acylguanidines was designed, synthesized and evaluated for their protective effect on injured vascular endothelial cell (ECV-304). The preliminary results demonstrated that some compounds possessed more potent activities than that of Ligustrazine in stimulating replication of the injured endothelial cell. Among the active compounds, compounds 8b, 8f and 8l displayed remarkable antioxidative activity with low EC50 values of 0.097, 0.059 and 0.094 mM, respectively. Structure-activity relationships were briefly discussed.
- Li, Zhenyu,Yu, Fang,Zhan, Peng,Shen, Yuemao,Liu, Xinyong,Cui, Lei,Wang, Shouxun
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p. 928 - 933,6
(2020/08/31)
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- Discovery of tetrasubstituted pyrazines as semiochemicals in a sexually deceptive orchid
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Sexually deceptive orchids employ mimicry of insect sex pheromones to exploit a diverse group of pollinators. The chemical structures of five semiochemicals (1-3, 7, 8) produced by populations of the warty hammer orchid, Drakaea livida, pollinated by a thynnine wasp in the genus Catocheilus were elucidated. With the exception of (2,5-dimethylpyrazin-3-yl)methyl 3-methylbutanoate (7), all active compounds were tetrasubstituted pyrazines, including hydroxymethyl (1) and ester (2 and 3) trimethylpyrazine derivatives. Male Catocheilus wasps were responsive to all of these compounds in GC-EAD experiments.
- Bohman, Bjoern,Jeffares, Lynne,Barrow, Russell A.,Phillips, Ryan D.,Peakall, Rod,Flematti, Gavin,Dixon, Kingsley W.,Byrne, Lindsay T.,Skelton, Brian W.
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p. 1589 - 1594,6
(2020/09/09)
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- Ligustrazine derivatives. Part 3: Design, synthesis and evaluation of novel acylpiperazinyl derivatives as potential cerebrocardiac vascular agents
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A series of novel acylpiperazinyl Ligustrazine derivatives was designed, synthesized, and their protective effects on damaged ECV-304 cells and antiplatelet aggregation activities were evaluated. The results showed that compound E33 displayed most potential protective effects on the ECV-304 cells damaged by hydrogen peroxide, and compound E1 was found to be the most active antiplatelet aggregation agent. Structure-activity relationships were briefly discussed.
- Cheng, Xian-Chao,Liu, Xin-Yong,Xu, Wen-Fang,Guo, Xiu-Li,Zhang, Ning,Song, Yu-Ning
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experimental part
p. 3018 - 3024
(2009/09/05)
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- Design, synthesis, and biological activities of novel Ligustrazine derivatives
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A series of novel Ligustrazine derivatives was designed, synthesized, and assayed for their protective effects on damaged ECV-304 cells and antiplatelet aggregation activities. The results showed that most Ligustrazine derivatives exhibited lower EC50 values for protective effects on the ECV-304 cells damaged by hydrogen peroxide in comparison with Ligustrazine. And some Ligustrazine derivatives presented better antiplatelet aggregation activities than Ligustrazine. The derivatives containing the bisphenylmethyl pharmacophore (7a-c) exhibited highest potency. Compound 7a displayed most potential protective effects on the ECV-304 cells damaged by hydrogen peroxide, and compound 7c was found to be the most active antiplatelet aggregation agent. Structure-activity relationships were briefly discussed.
- Cheng, Xian-Chao,Liu, Xin-Yong,Xu, Wen-Fang,Guo, Xiu-Li,Ou, Yang
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p. 3315 - 3320
(2008/02/07)
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- The preparation of novel ligustrazine derivatives as potential cerebrocardiac vascular agents
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A series of novel substituted cinnamoylpiperazinyl ligustrazine derivatives 7 has been prepared by alkylation of cinnamoylpiperazines by (chloromethyl)trimethylpyrazine (5) or by cinnamoylation of trimethyl(piperazinomethyl) pyrazine (6).
- Cheng, Xian-Chao,Liu, Xin-Yong,Xu, Wen-Fang
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p. 577 - 579
(2007/10/03)
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- Synthesis of the novel liqustrazine derivatives and their protective effect on injured vascular endothelial cell damaged by hydrogen peroxide
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A series of novel 2-acyloxymethyl-3,5,6-trimethylpyrazine derivatives was designed and synthesized. Most compounds were found to be 1.5-4.5-fold higher potency than tetramethylpyrazine (TMP) in stimulating the proliferation of normal vascular endothelial cells and in protecting against hyperoxic acute injury. The most active one is the 2-nicotinoyl ester 5a exhibiting the maximum proliferation rate (Pmax) of 88.57% at the concentration of 0.1 mmol L-1. Structure-activity relationships of these compounds were discussed.
- Liu, Xinyong,Zhang, Rui,Xu, Wenfang,Li, Chaowu,Zhao, Quanqin,Wang, Xingpo
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p. 2123 - 2126
(2007/10/03)
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- (2,6)- and (2,5)Pyrazinophanes: Synthesis and Molecular Structure
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The title compounds 1-3 and their methyl derivatives 4-7 were synthesized either by photolytic sulfur extrusion from the corresponding 2,11-dithiapyrazinophanes 24-26 or by Hofmann 1,6-elimination of the appropriate trimethylammonium hydroxides followed by dimerization of the generated 2,5-dihydro-2,5-dimethylene-pyrazines. α-Chlorination of the methylpyrazines 8-10 with N-chlorosuccinimide gave the required precursors 11, 12, 14, 17, and 18.The results of the X-ray structure determinations for 1-4 and 7 which indicate an unequivocal isomer assignment are discussed with regard to steric strain in these molecules.The electronic spectra of the pyrazinophanes 1-7 are reported and compared with those of the parent methylpyrazines.
- Eiermann, Uwe,Krieger, Claus,Neugebauer, Franz A.,Staab, Heinz A.
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p. 523 - 533
(2007/10/02)
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- Polyheterocyclic compounds
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This invention provides polyheterocyclic compound useful as a flavorant additive. In one embodiment, this invention provides a polyheterocyclic flavorant additive for smoking compositions such as 1,2-bis(3,5,6-trimethyl-2-pyrazyl)ethane: STR1 Under smoking conditions the above illustrated polyheterocyclic additive flavors the mainstream and sidestream smoke. In another embodiment, this invention provides a polyheterocyclic such as 1-(3,5,6-trimethyl-2-pyrazyl)-2-(2-pyridyl)ethane.
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- The Reaction of Alkylpyrazine Anions with Some Electrophiles. Synthesis of 1,2-bis(2-pyrazyl)ethanes
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The reaction of alkylpyrazine anions with iodine, 1,2-dibromoethylene or oxygen gives 1,2-bis(2-pyrazyl)ethanes.
- Houminer, Yoram,Sanders, Edward B.
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p. 647 - 649
(2007/10/02)
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