260417-55-8Relevant academic research and scientific papers
Half-sandwich ruthenium complex containing phenyl benzoxazole structure as well as preparation method and application of half-sandwich ruthenium complex
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Paragraph 0065-0068, (2021/04/14)
The invention relates to a half-sandwich ruthenium complex containing a phenyl benzoxazole structure as well as a preparation method and application of the half-sandwich ruthenium complex. The ruthenium complex has the following structure as shown in the specification. The preparation method comprises the steps of dissolving phenyl benzoxazole, [CymRuCl2] 2 and sodium acetate in methanol at room temperature, heating the system, and continuing to react; and after the reaction is finished, standing, filtering, carrying out reduced pressure pumping on the solvent, carrying out column chromatography separation on the obtained crude product to obtain the red half-sandwich ruthenium complex containing the phenyl benzoxazole structure, and applying the red half-sandwich ruthenium complex to catalysis of oxidation of alkyl pyridine compounds to prepare nitrogen heterocyclic ketone compounds. Compared with the prior art, the preparation method provided by the invention is simple and green, the catalytic oxidation reaction can be carried out under mild conditions, and the catalyst has high stability and is not sensitive to air and water.
Analogues of fenarimol are potent inhibitors of trypanosoma cruzi and are efficacious in a murine model of chagas disease
Keenan, Martine,Abbott, Michael J.,Alexander, Paul W.,Armstrong, Tanya,Best, Wayne M.,Berven, Bradley,Botero, Adriana,Chaplin, Jason H.,Charman, Susan A.,Chatelain, Eric,Von Geldern, Thomas W.,Kerfoot, Maria,Khong, Andrea,Nguyen, Tien,McManus, Joshua D.,Morizzi, Julia,Ryan, Eileen,Scandale, Ivan,Thompson, R. Andrew,Wang, Sen Z.,White, Karen L.
, p. 4189 - 4204 (2012/07/27)
We report the discovery of nontoxic fungicide fenarimol (1) as an inhibitor of Trypanosoma cruzi (T. cruzi), the causative agent of Chagas disease, and the results of structure-activity investigations leading to potent analogues with low nM IC50s in a T. cruzi whole cell in vitro assay. Lead compounds suppressed blood parasitemia to virtually undetectable levels after once daily oral dosing in mouse models of T. cruzi infection. Compounds are chemically tractable, allowing rapid optimization of target biological activity and drug characteristics. Chemical and biological studies undertaken in the development of the fenarimol series toward the goal of delivering a new drug candidate for Chagas disease are reported.
A Novel Approach to Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors Based on the Link of 1,3-Dioxane-Thromboxane Receptor Antagonists and -Thromboxane Synthase Inhibitors
Ackerley, Norman,Brewster, Andrew G.,Brown, George R.,Clarke, David S.,Foubister, Alan J.,et al.
, p. 1608 - 1628 (2007/10/02)
A new class of dual-acting racemic thromboxane receptor antagonist/thromboxane synthase inhibitors is reported, based on the novel approach of linking the known thromboxane synthase inhibitors (TXSI) dazoxiben (2) or isbogrel (11) (separately) to thromboxane receptor antagonists (TXRA) from the 1,3-dioxane series, such as ICI 192605 (10).Dual activity was observed in vitro with inhibition of human microsomal thromboxane synthase in the range IC50 = 0.01-1.0 μM and receptor antagonist activity by inhibition of U46619-induced human platelet aggregation in the range pA2 = 5.5-7.0.The in vitro results also showed that very large groups could be tolerated at the selected substitution positions of the TXRA and TXSI components.Oral activity was observed in ex vivo tests in both rats and dogs at a dose of 10 mg/kg.Thus, (E)-7--4-(2-hydroxyphenyl)-1,3-dioxan-2-yl>benzyl>oxy>phenyl>-7-(3-pyridyl)hept-6-enoic acid (110) was both an antagonist (pA2 = 6.7) and a synthase inhibitor (IC50 = 0.02 μM)).On oral dosing (10 mg/kg) to rats and dogs, 110 showed significant TXRA activity 64 (rat, 3 h) and >59 +/- 11.3 (dog, 2 h) vs ex vivo U46619-induced platelet aggregation>.Inhibition of thromboxane synthase at the respective time points in these experiments was 81 +/- 4.4percent (rat) and 69 +/- 4.8percent (dog).
