61439-59-6Relevant academic research and scientific papers
A new multifunctional hydroxytyrosol-fenofibrate with antidiabetic, antihyperlipidemic, antioxidant and antiinflammatory action
Xie, Yundong,Xu, Yanhong,Chen, Zizhang,Lu, Wenfang,Li, Na,Wang, Qiutang,Shao, Lihua,Li, Yiping,Yang, Guangde,Bian, Xiaoli
, p. 1749 - 1758 (2017)
Dyslipidemia, oxidative stress and inflammation are major risky factors involved in the pathophysiology of type 2 diabetes mellitus and atherosclerosis. Multifunctional intervene is more meaningful. The aim of this study was to evaluate the multifunctional effects of two new compounds, combination of fenofibric acid (FA) with tyrosol (T) or hydroxytyrosol (HT). Compared with fenofibrate (FF), FF-HT exhibited excellent antioxidant capacities in vitro and much improved hypolipidemia, reducing plasma triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 76%, 54%, and 28%, while FF-T decreased the plasma parameters by 16%, 10%, and 20% in hyperlipidemic mice induced by Triton WR 1339. Furthermore, compound FF-HT exhibited significant antihyperglycemic, antihyperlipidemic, antioxidant and anti-inflammatory activities as well as attenuating hepatotoxicity in a type 2 diabetes experimental mouse model. The histological findings showed that FF-HT suppressed the development of hepatic lipid accumulation and ameliorated the damage in hepatic and pancreatic tissues compared to model mice. This study indicates for the first time that reasonable optimized drug design produce a compound entity which is conducive to the prevention of type 2 diabetes mellitus and its complications.
Straightforward access to novel mitochondriotropics derived from 2-arylethanol as potent and selective antiproliferative agents
Hicke, Francisco J.,Puerta, Adrián,Dini?, Jelena,Pe?i?, Milica,Padrón, José M.,López, óscar,Fernández-Bola?os, José G.
, (2021/12/01)
The necessity for developing novel cytostatic agents with improved activities and reduced side-effects to tackle cancer prompted us to investigate mitochondria-targeted compounds, an approach that is gaining attention for the selective transportation of cytotoxic agents. We envisioned the possibility of conjugating a phenethyl alcohol motif, decorated with a series of phenol-based substituents on the aryl moiety, with a triphenyl phosphonium scaffold (a mitochondria-directed vector), through a hydrocarbon chain of different lengths. Thus, such compounds that incorporate the phenethyl skeleton can be considered as masked phenolic compounds derived from relevant natural counterparts found in olive tree (e.g. tyrosol, hydroxytyrosol). Title compounds exhibited very strong in vitro antiproliferative activities against the panel of six human tumor cell lines tested, with GI50 values ranging from the nanomolar (0.026 ± 0.010 μM for 36) to the submicromolar range in most of the cases; this represents an improvement of up to 350-fold compared to classical chemotherapeutic agents, like 5-fluorouracil or cisplatin. Interestingly, decrease in the linker length led to an increase of GI50 values against non-tumor cells, thus allowing a remarkable improvement of selectivity (SI up to 269). The very promising antiproliferative activities prompted us to further investigate their behaviour against multidrug resistant cell lines (MDR). The results indicated a reduced sensitivity of the multidrug resistant cells to compounds, probably due to P-gp-mediated efflux of these antiproliferative agents. Interestingly, activities were completely restored to the same levels by co-administration of tariquidar, a well-known inhibitor of P-gp. Flow cytometry analysis on sensitive cell lines revealed a decrease in the percentage of cells in G1 phase accompanied by increase in S and G2/M phases. In addition, a significant increase in subG1 area, was observed. These results are compatible with the necrotic and apoptotic cell death detected in the Annexin V assay, and with the depolarization of the mitochondria membrane. Thus, the new mitochondriotropic agents reported herein can be considered as promising antiproliferative agents, endowed with remarkable potency and selectivity, including MDR cells, upon co-administration with a pump-efflux inhibitor.
Preparation method of 2-(4-benzyloxyphenyl)ethanol
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, (2021/08/06)
The invention provides a preparation method of 2-(4-benzyloxyphenyl)ethanol. The preparation method comprises the following steps: 1) subjecting phenol to reacting with chloroacetyl chloride under the catalysis of aluminum trichloride to obtain a compound as shown in a formula II; 2) subjecting the compound as shown in the formula II to reacting with benzyl halide under an alkaline condition to obtain a compound as shown in a formula III, wherein the benzyl halide is one selected from benzyl bromide and benzyl chloride; 3) performing reduction treatment on the compound as shown in the formula III, and adjusting a reaction system to be an alkaline system to obtain a compound as shown in a formula IV; and 4) under the action of a catalyst, reducing the compound as shown in the formula IV under a hydrogen condition to obtain the 2-(4-benzyloxyphenyl)ethanol as shown in the formula I. The preparation method has the advantages of low cost, mild reaction conditions, safety in operation and less three-waste pollution, and is beneficial to being applied to industrial production.
Synthesis and structure activity relationships of cyanopyridone based anti-tuberculosis agents
Boshoff, Helena I. M.,Caljon, Guy,Forbes, He Eun,Hulpia, Fabian,Jian, Yanlin,Munier-Lehmann, Héle?ne,Risseeuw, Martijn D. P.,Van Calenbergh, Serge
, (2020/07/06)
Mycobacterium tuberculosis, the causative agent of tuberculosis, relies on thymidylate kinase (MtbTMPK) for the synthesis of thymidine triphosphates and thus also DNA synthesis. Therefore, this enzyme constitutes a potential Achilles heel of the pathogen. Based on a previously reported MtbTMPK 6-aryl-substituted pyridone inhibitor and guided by two co-crystal structures of MtbTMPK with pyridone- and thymine-based inhibitors, we report the synthesis of a series of aryl-shifted cyanopyridone analogues. These compounds generally lacked significant MtbTMPK inhibitory potency, but some analogues did exhibit promising antitubercular activity. Analogue 11i demonstrated a 10-fold increased antitubercular activity (MIC H37Rv, 1.2 μM) compared to literature compound 5. Many analogues with whole-cell antimycobacterial activity were devoid of significant cytotoxicity.
Butenolide derivative as well as preparation method and application thereof
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Paragraph 0052-0054; 0056, (2020/07/21)
The invention discloses a butenolide compound as well as a preparation method and an application thereof. The butenolide derivative has the inhibitory activity of protein tyrosine phosphatase 1B (PTP1B), improves insulin resistance of HepG2 cells, generates a remarkable hypoglycemic effect and can be used for preparing a medicine for treating diabetes mellitus.
1-(4-(2-cyclobutoxyethyl) phenoxy)-3-(isopropylamino) propyl-2-ol and preparation method thereof
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Paragraph 0007-0008; 0024-0026, (2020/10/14)
The invention belongs to the technical field of medicine preparation, and mainly relates to a new compound 1-(4-(2-cyclobutoxyethyl) phenoxy)-3-(isopropylamino) propyl-2-ol, a preparation method and application in detection of betaxolol hydrochloride and betaxolol hydrochloride eye drops related substances. The structure of the compound is as shown in the specification. The 1-(4-(2-cyclobutoxyethyl) phenoxy)-3-(isopropylamino) propyl-2-ol prepared by the preparation method disclosed by the invention can be used as a reference substance for detecting the content of 1-(4-(2-cyclobutoxyethyl) phenoxy)-3-(isopropylamino) propyl-2-ol in betaxolol hydrochloride and eye drops of betaxolol hydrochloride. Technical support and material guarantee are provided for improving the quality standard of betaxolol hydrochloride and eye drops thereof and controlling the safety of product quality, so that the national standard of betaxolol hydrochloride is at the world leading level, and the product has good economic benefits and social benefits.
Access to β-Ketonitriles through Nickel-Catalyzed Carbonylative Coupling of α-Bromonitriles with Alkylzinc Reagents
Donslund, Aske S.,Neumann, Karoline T.,Corneliussen, Nicklas P.,Grove, Ebbe K.,Herbstritt, Domenique,Daasbjerg, Kim,Skrydstrup, Troels
supporting information, p. 9856 - 9860 (2019/07/09)
Herein, we report a nickel-catalyzed carbonylative coupling of α-bromonitriles and alkylzinc reagents with near stoichiometric carbon monoxide to give β-ketonitriles in good yields. The reaction is catalyzed by a readily available and stable nickel(II) pincer complex. The developed protocol tolerates substrates bearing a variety of functional groups, which would be problematic or incompatible with previous synthetic methods. Additionally, we demonstrate the suitability of the method for carbon isotope labeling by the synthesis of 13C-labeled β-ketonitriles and their transformation into isotopically labeled heterocycles.
A New Series of Salicylic Acid Derivatives as Non-saccharide α-Glucosidase Inhibitors and Antioxidants
Chen, Jiangang,Lu, Wenfang,Chen, Hao,Bian, Xiaoli,Yang, Guangde
, p. 231 - 246 (2019/02/19)
In this study, a series of salicylic acid derivatives were designed and synthesized as novel non-saccharide α-glucosidase inhibitors. Biological evaluation indicated that when compared to acarbose, compounds T9, T10, and T32 exhibited a higher potency of α-glucosidase inhibitory activity with IC50 values of 0.15±0.01, 0.086±0.01 and 0.32±0.02mM, respectively. Evaluation of the inhibition kinetics indicated that T9, T10, T32, and acarbose interacted with α-glucosidase in a mixed non-competitive inhibitory manner. Moreover, T9, T10, and T32 statically quenched the fluorescence of α-glucosidase by formation of an inhibitor-α-glucosidase complex. The docking results showed that hydrogen bonds were generated between the test compounds and α-glucosidase. The antioxidant study revealed that compound T10 exhibited a higher antioxidant activity via scavenging 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH), thereby inhibiting lipid peroxidation and the total reduction capacity. In brief, the salicylic acid derivatives identified in this study were promising candidates for development as novel non-saccharide α-glucosidase inhibitors.
α-Amino Diphenyl Phosphonates as Novel Inhibitors of Escherichia coli ClpP Protease
Moreno-Cinos, Carlos,Sassetti, Elisa,Salado, Irene G.,Witt, Gesa,Benramdane, Siham,Reinhardt, Laura,Cruz, Cristina D.,Joossens, Jurgen,Van Der Veken, Pieter,Br?tz-Oesterhelt, Heike,Tammela, P?ivi,Winterhalter, Mathias,Gribbon, Philip,Windshügel, Bj?rn,Augustyns, Koen
, p. 774 - 797 (2019/01/30)
Increased Gram-negative bacteria resistance to antibiotics is becoming a global problem, and new classes of antibiotics with novel mechanisms of action are required. The caseinolytic protease subunit P (ClpP) is a serine protease conserved among bacteria that is considered as an interesting drug target. ClpP function is involved in protein turnover and homeostasis, stress response, and virulence among other processes. The focus of this study was to identify new inhibitors of Escherichia coli ClpP and to understand their mode of action. A focused library of serine protease inhibitors based on diaryl phosphonate warheads was tested for ClpP inhibition, and a chemical exploration around the hit compounds was conducted. Altogether, 14 new potent inhibitors of E. coli ClpP were identified. Compounds 85 and 92 emerged as most interesting compounds from this study due to their potency and, respectively, to its moderate but consistent antibacterial properties as well as the favorable cytotoxicity profile.
Exploring physicochemical space: Via a bioisostere of the trifluoromethyl and ethyl groups (BITE): Attenuating lipophilicity in fluorinated analogues of Gilenya for multiple sclerosis
Erdeljac, Nathalie,Kehr, Gerald,Ahlqvist, Marie,Knerr, Laurent,Gilmour, Ryan
, p. 12002 - 12005 (2018/11/21)
The direct, catalytic vicinal difluorination of terminal alkenes via an I(i)/I(iii) manifold was exploited to install a chiral, hybrid bioisostere of the CF3 and Et groups (BITE) in Gilenya; the first orally available drug for the clinical management of Multiple Sclerosis (MS). This subtle fluorination pattern allows lipophilicity (logD) to be tempered compared to the corresponding CF3 and Et derivatives (CH2CH3 > CH2CF3 > CHFCH2F).
