882-09-7Relevant academic research and scientific papers
Simultaneous GLC determination of clofibrate and clofibric acid in human plasma
Wolf,Zimmerman
, p. 92 - 93 (1980)
A simultaneous assay for the detection of clofibrate and its metabolite, clofibric acid [2-(p-chlorophenoxy)-2-methylpropionic acid], is described. This GLC method is rapid and does not require a derivatization step. It is sensitive to 1-μg/ml levels of either compound in biological samples and can be used to characterize the in vivo conversion of clofibrate ester to the free acid.
The combination of sesamol and clofibric acid moieties leads to a novel potent hypolipidemic agent with antioxidant, anti-inflammatory and hepatoprotective activity
Xie, Yundong,Liu, Jiping,Shi, Yongheng,Wang, Bin,Wang, Xiaoping,Wang, Wei,Sun, Meng,Xu, Xinya,Jiang, Haihui,Guo, Min,He, Yiyi,Ren, Cuicui,Cheng, Lifei
, (2021)
Oxidative stress and inflammation have been considered the main factors in the liver injury of clofibrate (CF). To obtain a novel antihyperlipidemic agent with antioxidant, anti-inflammation and hepatoprotection, the combination of sesamol and clofibric acid moieties was performed and achieved sesamol-clofibrate (CF-Sesamol). CF-Sesamol showed significant hypolipidemia effects in hyperlipidemia mice induced by Triton WR 1339, reducing TG by 38.8% (P 0.01) and TC by 35.1% (P 0.01). CF-Sesamol also displayed an alleviating effect on hepatotoxicity. The hepatic weight and hepatic coefficient were decreased. The amelioration of liver function was observed, such as aspartate and lactate transaminases (AST and ALT), alkaline phosphatase (ALP) and total proteins (TP) levels. Liver histopathological examination showed that hepatocyte necrosis, cytoplasmic loosening, nuclear degeneration and inflammatory cell infiltration reduced obviously by treatment with CF-Sesamol. Related molecular mechanisms on hepatoprotection showed that CF-Sesamol up-regulated Nrf2 and HO-1 expression and down-regulated p-NF-κB p65 expression in hepatic tissues. CF-Sesamol has significant antioxidant and anti-inflammatory effects. Plasma antioxidant enzymes such as SOD and CAT increased, anti-lipid peroxidation product MDA decreased. The expression of TNF-α and IL-6 inflammatory cytokines in liver was significantly lower than that in the CF group. The results indicated that CF-Sesamol exerted more potent antihyperlipidemic effects and definite hepatoprotective activity partly through the Nrf2/NF-κB-mediated signaling pathway.
The formation of benzoxacin-3-ones: Via intramolecular Nicholas reactions and synthesis of 8-membered heliannuols
Green, James R.,St. Onge, Brent
supporting information, p. 7152 - 7155 (2021/08/30)
The γ-carbonyl cations generated from propargyl ether-Co2(CO)6 complexes undergo intramolecular Nicholas reactions to give dehydrobenzoxacin-3-one-Co2(CO)6 complexes in good yields. Reductive decomplexation and subsequent manipulation allows the synthesis of (±)-heliannuol K methyl ether and the formal syntheses of (±)-heliannuol K, (±)-heliannuol A, and (-)-heliannuol L.
INHIBITORS TO TARGET HIV-1 NEF-CD80/CD86 INTERACTIONS FOR THERAPEUTIC INTERVENTION
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Paragraph 000169; 000186; 000187; 000189, (2020/03/05)
The compounds of Formula I, II, and III along with their stereoisomers, pharmaceutically acceptable salts, polymorphs, solvates and hydrates thereof are described in the present disclosure. The said compounds restore immune activation in case of infections or a disease associated with an HIV infection in a subject in need thereof.
Diester compounds of PPAR protein activator
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Paragraph 0056-0064, (2020/12/15)
The invention relates to diester compounds of a PPAR protein activator. The compounds are compounds shown in the formula (I) and pharmaceutically acceptable salts, prodrugs and solvates thereof, and apharmaceutical composition comprising the compounds and a synthesis method thereof. Furthermore, the invention relates to pharmaceutical composition comprising the compounds, and the pharmaceutical composition can be used for the prevention or treatment on diseases associated with PPPAR proteins.
Piperazine adenosine monophosphate activated protein kinase (AMPK) agonist and medical application thereof
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Paragraph 0147; 0149; 0151, (2019/11/12)
The invention discloses a piperazine compound with AMPK agonist activity, and a preparation method and medical application of the piperazine compound. The piperazine compound is a compound shown as aformula (I) (please see the specifications for the formula), and a pharmaceutically acceptable salt or ester or a prodrug or N-oxide or solvate thereof. The compound can be used for preparing drugs for preventing or treating AMPK-mediated diseases.
Decarboxylative Giese-Type Reaction of Carboxylic Acids Promoted by Visible Light: A Sustainable and Photoredox-Neutral Protocol
Ramirez, Nieves P.,Gonzalez-Gomez, Jose C.
supporting information, p. 2154 - 2163 (2017/04/24)
We describe herein a transition-metal-free method for the decarboxylative generation of radicals from carboxylic acids and their 1,4-addition to Michael acceptors. The Fukuzumi catalyst (9-mesitylene-10-methylacridinium perchlorate, [Acr-Mes]ClO4) enabled this transformation under visible-light irradiation at room temperature with CO2 as the only byproduct. The scope and limitations of this protocol were examined by using a range of Michael acceptors (15 examples) and carboxylic acids (18 examples). The use of 3-hydroxypivalic acid in this protocol allowed the straightforward formation of a diastereomerically pure δ-lactone. Moreover, when a homoallylic acid was used, a radical cascade reaction took place with the formation of three C–C bonds.
Design, synthesis of novel, potent, selective, orally bioavailable adenosine A2A receptor antagonists and their biological evaluation
Basu, Sujay,Barawkar, Dinesh A.,Thorat, Sachin,Shejul, Yogesh D.,Patel, Meena,Naykodi, Minakshi,Jain, Vaibhav,Salve, Yogesh,Prasad, Vandna,Chaudhary, Sumit,Ghosh, Indraneel,Bhat, Ganesh,Quraishi, Azfar,Patil, Harish,Ansari, Shariq,Menon, Suraj,Unadkat, Vishal,Thakare, Rhishikesh,Seervi, Madhav S.,Meru, Ashwinkumar V.,De, Siddhartha,Bhamidipati, Ravi K.,Rouduri, Sreekanth R.,Palle, Venkata P.,Chug, Anita,Mookhtiar, Kasim A.
supporting information, p. 681 - 694 (2017/02/05)
Our initial structure-activity relationship studies on 7-methoxy-4-morpholino-benzothiazole derivatives featured by aryloxy-2-methylpropanamide moieties at the 2-position led to identification of compound 25 as a potent and selective A2A adenosine receptor (A2AAdoR) antagonist with reasonable ADME and pharmacokinetic properties. However, poor intrinsic solubility and low to moderate oral bioavailability made this series unsuitable for further development. Further optimization using structure-based drug design approach resulted in discovery of potent and selective adenosine A2A receptor antagonists bearing substituted 1-methylcyclohexyl-carboxamide groups at position 2 of the benzothiazole scaffold and endowed with better solubility and oral bioavailability. Compounds 41 and 49 demonstrated a number of positive attributes with respect to in vitro ADME properties. Both compounds displayed good pharmacokinetic properties with 63% and 61% oral bioavailability, respectively, in rat. Further, compound 49 displayed oral efficacy in 6-OHDA lesioned rat model of Parkinson diseases.
Method for synthesizing clofibrate drug intermediate 2-(4-Chlorophenoxy)-2-methylpropionic acid
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Paragraph 0005; 0013; 0014, (2016/11/21)
A method for synthesizing a clofibrate drug intermediate 2-(4-Chlorophenoxy)-2-methylpropionic acid includes the following steps that 0.62 mol of p-chloro phenoxy solution, 300 ml of hexane, 500 ml of sodium sulfite solution and 0.71-0.73 mol of acetamide solution are added into a reaction container provided with a stirrer, a thermometer, a backflow condenser and a dropping funnel, the stirring speed is controlled to be 130-160 rpm, the solution temperature is raised to 60-65 DEG C, 0.75-0.79 mol of 1-bromine-methanediamine solution is added dropwise, reflux is maintained for 90-130 min after addition, an oxalic acid is added to adjust the pH value of the solution to be 4-5, the solution temperature is reduced to 3-7 DEG C, solid is separated out, filtered, washed with a saline solution, propionitrile and ethylenediamine, dehydrated through a dehydrating agent and recrystallized in nitromethane, and crystal of 2-(4-Chlorophenoxy)-2-methylpropionic acid is obtained.
Pd(II)-catalyzed ortho - Or meta-C-H olefination of phenol derivatives
Dai, Hui-Xiong,Li, Gang,Zhang, Xing-Guo,Stepan, Antonia F.,Yu, Jin-Quan
supporting information, p. 7567 - 7571 (2013/06/27)
A combination of weakly coordinating auxiliaries and ligand acceleration allows for the development of both ortho- and meta-selective C-H olefination of phenol derivatives. These reactions demonstrate the feasibility of directing C-H functionalizations when functional groups are distal to target C-H bonds. The meta-C-H functionalization of electron-rich phenol derivatives is unprecedented and orthogonal to previous electrophilic substitution of phenols in terms of regioselectivity. These methods are also applied to functionalize α-phenoxyacetic acids, a fibrate class of drug scaffolds.
