125971-95-1Relevant articles and documents
[18F]Atorvastatin: synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action
Antunes, Inês F.,Clemente, Gon?alo S.,D?mling, Alexander,Elsinga, Philip H.,Rickmeier, Jens,Ritter, Tobias,Zarganes-Tzitzikas, Tryfon
, (2020/04/24)
Background: Statins are lipid-lowering agents that inhibit cholesterol synthesis and are clinically used in the primary and secondary prevention of cardiovascular diseases. However, a considerable group of patients does not respond to statin treatment, and the reason for this is still not completely understood. [18F]Atorvastatin, the 18F-labeled version of one of the most widely prescribed statins, may be a useful tool for statin-related research. Results: [18F]Atorvastatin was synthesized via an optimized ruthenium-mediated late-stage 18F-deoxyfluorination. The defluoro-hydroxy precursor was produced via Paal-Knorr pyrrole synthesis and was followed by coordination of the phenol to a ruthenium complex, affording the labeling precursor in approximately 10% overall yield. Optimization and automation of the labeling procedure reliably yielded an injectable solution of [18F]atorvastatin in 19% ± 6% (d.c.) with a molar activity of 65 ± 32 GBq·μmol?1. Incubation of [18F]atorvastatin in human serum did not lead to decomposition. Furthermore, we have shown the ability of [18F]atorvastatin to cross the hepatic cell membrane to the cytosolic and microsomal fractions where HMG-CoA reductase is known to be highly expressed. Blocking assays using rat liver sections confirmed the specific binding to HMG-CoA reductase. Autoradiography on rat aorta stimulated to develop atherosclerotic plaques revealed that [18F]atorvastatin significantly accumulates in this tissue when compared to the healthy model. Conclusions: The improved ruthenium-mediated 18F-deoxyfluorination procedure overcomes previous hurdles such as the addition of salt additives, the drying steps, or the use of different solvent mixtures at different phases of the process, which increases its practical use, and may allow faster translation to clinical settings. Based on tissue uptake evaluations, [18F]atorvastatin showed the potential to be used as a tool for the understanding of the mechanism of action of statins. Further knowledge of the in vivo biodistribution of [18F]atorvastatin may help to better understand the origin of off-target effects and potentially allow to distinguish between statin-resistant and non-resistant patients.
Atorvastatin calcium intermediate as well as preparation method and application thereof
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, (2019/04/04)
The invention discloses an atorvastatin calcium intermediate as well as a preparation method and application thereof. A synthesis process of the intermediate is environmentally-friendly, simple to operate and low in EHS risk; raw materials are easy to obtain; a used chemical reagent is small in toxicity and low in cost; and the synthesis process is a green synthesis process suitable for the industrial production. Moreover, the intermediate provided by the invention is applied to the synthesis of atorvastatin calcium and a key intermediate thereof, the route is relatively short, the yield is high, the industrial production cost of the atorvastatin calcium is effectively reduced, and the atorvastatin calcium intermediate has a relatively high industrial application prospect.
Separating method for impurity A and impurity B and method for effectively reducing content of impurity A in atorvastatin calcium condensate
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Paragraph 0071; 0072; 0073, (2019/01/16)
The invention discloses a separating method for an impurity A and an impurity B and a method for effectively reducing the content of an impurity A in an atorvastatin calcium condensate, and belongs tothe technical field of impurity separating in medicinal chemistry. The invention specifically discloses the impurity A in the atorvastatin calcium condensate, and a method for separating the impurityA from the atorvastatin calcium condensate, further studies that the impurity A of the atorvastatin calcium condensate is introduced by the impurity B in a starting material ATS-9 crude product, anddiscloses a method for separating the impurity B in the ATS-9 crude product, so as to reduce the content of impurity A in the atorvastatin calcium condensate, and further provide the basis for reducing the content of impurities in atorvastatin calcium diamine. The purity of the impurity A in the atorvastatin calcium condensate obtained by the separating method is at least 99.5%, and the purity ofthe impurity B in ATS-9 is at least 99.5%.