- Method for preparing rosuvastatin and pitavastatin 2, 5-diene heptanoate compound
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The invention discloses a method for preparing rosuvastatin and pitavastatin 2, 5-diene heptanoate compound. (4R, 6S)-6-[(1E)-2-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl (methanesulfonyl)amino]-5-pyrimidine] vinyl]-2,2-dimethyl-1,3-dioxane-4-tert-butyl acetate and (4R, 6S)-6-[[(1E)-2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl] vinyl]-2, 2-dimethyl-1, 3-dioxane-4-tert-butyl acetate are respectivelytaken as starting materials of rosuvastatin and pitavastatin, deprotection and a hydrolyzation one-step method is adopted to prepare statin acid, then the statin acid is taken as a reaction substratefor dehydration and substitution two-step reaction to prepare the 2, 5-diene heptanoate compound. The preparation and synthesis routes of rosuvastatin and pitavastatin 2, 5-diene heptanoate involved in the invention are short and feasible, the operation is simple and convenient, the product yield is high, and the rosuvastatin and pitavastatin 2, 5-diene heptanoate is more suitable for large-scaleindustrial production.
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Paragraph 0031-0033
(2020/05/14)
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- Multi-substituted dihydroisoquinolines he the sandbank contains the fluorine derivative and use thereof
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The invention belongs to the field of pharmaceutical chemistry, and provides a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor. The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor is a polysubstituted miazine statin fluorine-containing modifier of 1-fluoro-3-hydroxypentanoic acid and its salt or ester formed after ring opening of 3-fluoro-caprolactone fragment and its lactone. The structural formula of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor is shown in the specification. A result of test of like compounds shows that the compounds have an HMG-CoA reductase activity inhibition effect, and can be used as a new-generation latent HMG-CoA reductase inhibitor.
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Paragraph 0135; 0136
(2018/06/04)
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- For production of the precursor [...]
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PROBLEM TO BE SOLVED: To provide a precursor compound of pitavastatin calcium excellent in safety and cost with high yield and high selectivity in a mild condition.SOLUTION: A method for producing a precursor compound of pitavastatin calcium of formula 1 is characterized by reacting a compound of formula 2 with a compound of formula 3 in the presence of an alkali metal salt selected from alkali metal carbonate, alkali metal acetate, and alkali metal propionate. (In the formulae, Ris a C-Calkyl group, and Ris an aryl group, an aralkyl group, or an alkyl group.)
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- Method for preparing pitavastatin lactone impurity
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The invention discloses a method for preparing pitavastatin lactone impurity. 4-(1-(4-chlorobenzoyl))-6-imino-3-methyl-1,4,6,7-tetrahydropyrazolo[3,4-D][1,3]thiazol-4-yl)-2-methoxyphenol is one main impurity during production of pitavastatin calcium. The impurity can be prepared through dehydration condensation of a compound (E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3R,5S-dihydroxy-6-heptenoic acid. The condensation reaction conditions are mild, the product purity is high, and research demand on pitavastatin calcium quality is satisfied.
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Paragraph 0007
(2016/11/17)
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- The synthesis of [18F]pitavastatin as a tracer for hOATP using the Suzuki coupling
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Fluorine-18 labeled radiotracers, such as [18F]fluorodeoxyglucose, can be used as practical diagnostic agents in positron emission tomography (PET). Furthermore, the properties of pharmaceuticals can be enhanced significantly by the introduction of fluorine groups into their original structures, and significant progress has been made during the last three decades towards the development of practical procedures for the introduction of fluorine. The replacement of the fluorine atoms present in pharmaceuticals with radioactive 18F atoms is a rational approach for designing novel PET tracers. As a fluorine-containing pharmaceutical agent, pitavastatin has attracted considerable interest from researchers working in the life sciences because it can act as an antihyperlipidemic agent as well as a substrate for hepatic organic anion transporting polypeptides (hOATP). With this in mind, it was envisaged that [18F]pitavastatin would be used as an excellent imaging agent for hOATP, which prompted us to investigate the synthesis of this agent. Herein, we report a practical method for the synthesis of [18F]pitavastatin by the Suzuki coupling reaction of p-iodofluorobenzene and a quinoline boronate derivative, with the desired product being formed in a radiochemical yield of 12 ± 3% (decay corrected from [18F]fluoride ions, n = 3). This journal is
- Yagi, Yusuke,Kimura, Hiroyuki,Arimitsu, Kenji,Ono, Masahiro,Maeda, Kazuya,Kusuhara, Hiroyuki,Kajimoto, Tetsuya,Sugiyama, Yuichi,Saji, Hideo
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p. 1113 - 1121
(2015/02/19)
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- PHARMACEUTICALLY ACCEPTABLE AMINE SALTS OF PITAVASTATIN
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The present invention relates to pharmaceutically acceptable amine salts of pitavastatin and a method for producing pharmaceutically acceptable amine salts of pitavastatin. Also provided are pharmaceutical compositions of these amine salts or solvates thereof, and methods of their use as HMG-CoA reductase inhibitors.
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- Process for Preparing Pitavastatin, Intermediates and Pharmaceuctically Acceptable Salts Thereof
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Processes for preparing pravastatin, intermediates and pharmaceutically acceptable salts thereof are provided Crystalline forms of pravastatin, intermediates and pharmaceutically acceptable salts thereof are also disclosed.
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- PITAVASTATIN SALTS
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The present disclosure includes salt of pitavastatin, and processes for their preparation and isolation. It further relates to crystalline forms of pitavastatin salts and hydrates thereof, and process for preparing an amorphous form of pitavastatin
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Page/Page column 23
(2012/08/27)
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- PROCESS FOR PREPARING STATINS
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Process for the preparation of β-ketoester synthetic intermediates useful in the preparation of statins, in particular Pitavastatin.
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Page/Page column 6
(2011/11/12)
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- Drug or Supplement Combination with Conjugated Linoleic Acid for Fat Loss in Mammals
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Food, feed or drug combinations with conjugated linoleic acid are described that cause enhanced fat loss in mammals more efficiently than any of the individual components of the combination. Food, feed, or drugs that activate AMP activated protein kinase, agonists of nuclear receptors that bind RXR in adipocytes, or statin inhibitors were found to be more effective for fat loss when combined with conjugated linoleic acid.
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- A new and efficient synthesis of the HMG-CoA reductase inhibitor pitavastatin
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A new synthetic method for the preparation of pravastatin is described. The approach circumvents various synthetic problems associated with the buildup of the 3,5-dihydroxy-C7 acid side chain of HMG-CoA reductase inhibitors (statins). The use of the C6-amide derivative 5 instead of ester derivatives in the coupling reaction with carboxaldehyde 8 (Scheme 3) prevents undesired side reactions, such as eliminations and retro-aldol reactions. The method provides synthetic statins, such as pitavastatin, in >99% ee and exceptionally high overall yield. The enantiomerically pure starting material, (3S)-3-{[(tert-butyl)dimethylsilyl]oxy}-5-oxo-5-{[(1S)-1-phenylethyl]amino} pentanoic acid (3c), is prepared by an improved procedure from 3-{[(tert-butyl)dimethylsilyl]oxy}glutaric anhydride (1) and (1S)-1-phenylethylamine (2c; Scheme 1).
- Acemoglu, Murat,Brodbeck, Andre,Garcia, Angel,Grimier, Dominique,Hassel, Marc,Riss, Bernhard,Schreiber, Robert
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p. 1069 - 1081
(2008/03/12)
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- Treatment of type 1 diabetes with PDE5 inhibitors
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The use of a PDE5 inhibitor without substantial PDE2 inhibiting activity, or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of Type 1 Diabetes. A method of treating Type 1 Diabetes in an individual suffering from Type 1 Diabetes, which method comprises administering to said individual an effective amount of a PDE5 inhibitor without substantial PDE2 inhibiting activity, or a pharmaceutically acceptable salt thereof.
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- Process for producing (3R,5S)-(E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-quinolin- 3-yl]-3, 5-dihydroxyhept-6-enic acid esters
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A process for producing a compound represented by the following formula (IV): (wherein R denotes a hydrogen atom, an alkyl group, or an aryl group), comprising reducing a compound selected from the group consisting of: a compound represented by the following formula (I): (wherein R is as defined in the formula); a compound represented by the following formula (II): (wherein R is as defined in the formula); and a compound represented by the following formula (III): (wherein R is as defined in the formula), by reacting the compound with a cell of a microorganism and/or a cell preparation thereof capable of stereo-selectively reducing a keto group.
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- Method for producing pharmaceutical dosage forms
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The invention relates to a method for producing a granulate while using spray-dried D-mannitol and to the production of pharmaceutical dosage forms comprised of granulates of this type. The invention additionally relates to granulates obtained by using this method and to pharmaceutical dosage forms, which contain statins, especially cerivastatin, and which can be produced from said granulates.
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- First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104
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First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104 are reported. A pair of syn diol isomers (NK-104 and its enantiomer) was obtained efficiently by diastereomeric resolution. The synthesis of a pair of anti diol isomers (3-epimer and 5-epimer) was accomplished effectively by the asymmetric aldol reaction followed by anti stereoselective reduction as key steps. Their purity determinations were effected by chiral HPLC analysis.
- Suzuki, Mikio,Yanagawa, Yoshinobu,Iwasaki, Hiroshi,Kanda, Hiroyasu,Yanagihara, Kazufumi,Matsumoto, Hiroo,Ohara, Yoshio,Yazaki, Yukari,Sakoda, Ryozo
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p. 2977 - 2982
(2007/10/03)
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- Stereoselective reduction of β,δ-diketo esters. A novel strategy for the synthesis of artificial HMG-CoA reductase inhibitors
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Condensation of N-methoxy-N-methyl amides with the dianions of acetoacetates gives in good yields β,δ-diketo esters, which are reduced with Et2BOMe-NaBH4 in tetrahydrofuran-methanol highly selectively to give syn-β,δ-dihydroxy esters in one step. Similarly, the β,δ-diketo esters of the Taber's chiral alcohol or its enantiomer respectively are reduced to give syn-β,δ-dihydroxy esters of moderate enantiomeric excess. Higher diastereo- and enantioselectivity were achieved by reduction of the β,δ-diketo esters of the Taber's chiral alcohol or its enantiomer successively with diisobutylalane and with Et2BOMe-NaBH4. The resulting syn-diol esters were hydrolyzed and lactonized to give various types of β-hydroxy-δ-lactones commonly found in artificial HMG-CoA reductase inhibitors.
- Hiyama,Reddy,Minami,Hanamoto
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p. 350 - 363
(2007/10/02)
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