85956-22-5Relevant articles and documents
Preparation method of oxidation impurities of hypolipidemic drugs
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Paragraph 0058-0059, (2021/05/12)
The invention discloses a preparation method of oxidation impurities of hypolipidemic drugs. The preparation method provided by the invention comprises the following step: in a solvent, under the action of an oxidizing agent and superfine silica powder, carrying out oxidation reaction as shown in the specification on a lactone compound as shown in a formula I to obtain a carbonyl compound as shown in a formula II. According to the preparation method disclosed by the invention, the superfine silica powder is adopted as a catalyst for oxidation reaction, so that the yield of the reaction is greatly improved.
Preparation method of oxidation impurities of hypolipidemic drugs
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Paragraph 0053; 0068-0069, (2021/05/12)
The invention discloses a preparation method of oxidation impurities of hypolipidemic drugs. The invention provides a preparation method of a phenol compound as shown in a formula III. The method comprises the following steps: (1) in a solvent and in the presence of acid, carrying out cyclization reaction as shown in the specification on a crude product of a sodium salt of a phenol compound as shown in a formula III' to obtain a phenol compound as shown in a formula IV; and (2) in a solvent, in the presence of alkali, carrying out a lactone ring-opening-salt forming reaction as shown in the specification on the phenol compound as shown in the formula IV to obtain the phenol compound as shown in the formula III. According to the preparation method, the pravastatin sodium oxide impurity with high purity can be obtained, the pravastatin sodium oxide impurity is used for product quality control, and the medication safety is improved.
The evaluation of statins as potential inhibitors of the LEDGF/p75-HIV-1 integrase interaction
Harrison, Angela T.,Kriel, Frederik H.,Papathanasopoulos, Maria A.,Mosebi, Salerwe,Abrahams, Shaakira,Hewer, Raymond
, p. 290 - 295 (2015/03/04)
Lovastatin was identified through virtual screening as a potential inhibitor of the LEDGF/p75-HIV-1 integrase interaction. In an AlphaScreen assay, lovastatin inhibited the purified recombinant protein-protein interaction (IC50 = 1.97 ± 0.45 μM) more effectively than seven other tested statins. None of the eight statins, however, yielded antiviral activity in vitro, while only pravastatin lactone yielded detectable inhibition of HIV-1 integrase strand transfer activity (31.65% at 100 μM). A correlation between lipophilicity and increased cellular toxicity of the statins was observed.
Capillary electrophoresis determination of pravastatin and separation of its degradation products
Nigovic, Biljana,Vegar, Ivana
experimental part, p. 615 - 622 (2009/12/03)
A capillary zone electrophoresis method for pravastatin determination was developed and validated. Rapid migration of negatively charged pravastatin molecule was obtained in alkaline buffer by the application of electric field of 30 kV. Influence of the pH value and ionic strength of running buffer, applied voltage and capillary temperature on mobility and sensitivity was evaluated. Detection wavelength was set to 237 nm. The method was applied to the determination of the drug in pharmaceutical dosage form. Pravastatin is a δ-hydroxy acid, which is prone to lactonize and epimerize in a pH-dependent manner. Micellar electrokinetic chromatographic approach was chosen to develop a method able to separate pravastatin and its degradation products in acidic media. The proposed method allows baseline separation of hydroxy acid and neutral lactone forms of the drug that appear as interconversion products depending on the pH value.
LACTONIZATION PROCESS
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Page/Page column 9, (2008/06/13)
The instant invention discloses a process for preparation of compound of formula (II) comprising treatment of compound of formula (I) with sulphuric acid, wherein the sulphuric acid is added in one portion, at less than 0.8 equivalents of compound of formula (I); at a temperature less than -150 C; for a time less than 1 hour; in a water miscible solvent, preferably acetonitrile, where G = unsubstituted or substituted alkyl, aryl or hetero aryl and X = H or metal or amine.
Selection of solid dosage form composition through drug-excipient compatibility testing
Serajuddin, Abu T. M.,Thakur, Ajit B.,Ghoshal, Rabin N.,Fakes, Michael G.,Ranadive, Sunanda A.,Morris, Kenneth R.,Varia, Sailesh A.
, p. 696 - 704 (2007/10/03)
A drug-excipient compatibility screening model was developed by which potential stability problems due to interactions of drug substances with excipients in solid dosage forms can be predicted. The model involved storing drug-excipient blends with 20% added water in closed glass vials at 50 °C and analyzing them after 1 and 3 weeks for chemical and physical stability. The total weight of drug-excipient blend in a vial was usually kept at about 200 mg. The amount of drug substance in a blend was determined on the basis of the expected drug-to-excipient ratio in the final formulation. Potential roles of several key factors, such as the chemical nature of the excipient, drug-to-excipient ratio, moisture, microenvironmental pH of the drug- excipient mixture, temperature, and light, on dosage form stability could be identified by using the model. Certain physical changes, such as polymorphic conversion or change from crystalline to amorphous form, that could occur in drug-excipient mixtures were also studied. Selection of dosage form composition by using this model at the outset of a drug development program would lead to reduction of 'surprise' problems during long-term stability testing of drug products.
Synthetic transformations of the mevinic acid nucleus: Preparation of a monocyclic analogue of compactin
Karanewsky
, p. 3911 - 3914 (2007/10/02)
The synthetic transformation of pravastatin into a fully functional, monocyclic analogue of compactin via a multistep sequence is described.
