- Preparation method of beraprost sodium
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The invention discloses a preparation method of a beraprost sodium intermediate. According to the preparation method, the synthesis route is shortened, the reaction condition is mild, and the operation is simple and convenient; the raw materials are cheap and easy to obtain, use of highly toxic and polluting reagents is avoided, and the cost is reduced; the product yield is obviously improved, and the method is suitable for industrial production.
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- Intermediate of beraprost and its salt and preparation method thereof
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The invention discloses an intermediate of beraprost and a salt thereof and a preparation method of the intermediate, and the preparation method has the advantages of mild reaction conditions. The method has the advantages of high selectivity, easiness in
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Paragraph 0255; 0279; 0666-0669
(2021/10/13)
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- Beraprost-314d crystals and methods for preparation thereof
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The present invention provides crystalline Forms II and III of Beraprost-314d, and processes for the preparation thereof.
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Page/Page column 8
(2020/03/18)
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- Beraprost-314d monohydrate crystals and methods for preparation thereof
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The present invention provides a monohydrated form of Beraprost-314d, and a novel crystalline form of Beraprost-314d monohydrate, and processes for the preparation thereof.
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Page/Page column 8-9
(2020/03/18)
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- Synthetic method of beraprost
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The invention relates to a synthetic method of beraprost. The synthetic method comprises the following steps: with an intermediate I as an initial raw material, carrying out selective primary alcoholoxidation and a Witting reaction to obtain an intermediate V; carrying out reduction and column chromatography purification on the intermediate V to obtain an intermediate IV; and hydrolyzing the intermediate IV to obtain beraprost. According to the synthetic method disclosed by the invention, two hydroxyl groups of the intermediate I are selectively oxidized, so a hydroxyl protection reagent is prevented from being used; in the oxidation step, ultralow-temperature (-60 to -80 DEG C) reactions and use of a reagent DCC with relatively high toxicity are avoided; in the reduction step, diisobutylaluminum hydride is prevented from being used; process operation units are greatly reduced, reaction steps are shortened, emission of three wastes is reduced, and the reactions are more efficient andenvironment-friendlier; and the main peak content of the prepared beraprost reaches 99.0% or above, and total process yield reaches 26% or above. The invention provides the synthetic method which ismore beneficial for industrial production.
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Paragraph 0059-0063; 0074-0076; 0077-0078; 0084
(2020/05/30)
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- Enantioselective Total Synthesis of Beraprost Using Organocatalyst
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A convergent and enantioselective total synthesis of the most active isomer of beraprost was achieved in 17 pots. A unique tricyclic core in beraprost was synthesized efficiently by utilizing the asymmetric organocatalyst-mediated formal [3 + 2] cycloaddi
- Umemiya, Shigenobu,Sakamoto, Daisuke,Kawauchi, Genki,Hayashi, Yujiro
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p. 1112 - 1115
(2017/03/14)
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- PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE BERAPROST
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The invention provides a new process for the preparation of optically active Beraprost of formula (I) starting from racemic Beraprost alkyl ester through hydrolysis, enantiomer esterification, preparation of diacyl -Beraprost ester diastereomers and their separation and hydrolysis.
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- Preparation method of Beraprost and its salt
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The invention relates to the technical field of medicine, in particular to a preparation method of Beraprost and its salt. The preparation method includes the steps of d), oxidizing a compound as shown in formula I-3 to prepare a compound as shown in formula IV, wherein the reaction equation is shown in the specification; e), and using IV compound as raw material to prepare the Beraprost or the salt of the Beraprost. The preparation method has the advantages that each reaction of the preparation process generates a single product, and the method is stable and controllable, environmentally friendly, good in yield, safe in process, and the like; the method is suitable for new drug research and development, capable of avoiding patent concentration, easy in refining and purification, easy in preparation and related impurity control, capable of optimizing a preparation process route and convenient to amplify.
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- METHODS FOR PRODUCING BERAPROST AND ITS DERIVATIVES
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The present invention is directed to methods for preparing Beraprost and novel synthetic intermediates for Beraprost. In one aspect, a process is provided to produce a pharmaceutical compound represented by the general Formula (I) via a radical cyclization route. The process is completed in fewer steps than the known synthetic methods and may be conducted to prepare commercially useful quantities. In another aspect, synthetic methods are provided for producing Beraprost and its derivatives,, which are stereoselective, efficient, scalable and economical. In another aspect, substantially isomerically pure compounds and intermediates are produced by the above processes.
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- METHOD OF PRODUCING BERAPROST
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An improved method is described for making single isomers of synthetic benzoprostacyclin analogue compounds, in particular the pharmacologically active 314-d isomer of beraprost. In contrast to the prior art, the method is stereoselective and requires few
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- THERAPY FOR COMPLICATIONS OF DIABETES
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A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.
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- ANTIHYPERTENSIVE THERAPY
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A new use of darusentan is provided in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy with one or more drugs. The composition comprises darusentan in an amount providing a therapeutically effective daily dose; wherein (a) the composition is orally deliverable and/or (b) the daily dose of darusentan is effective to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures. Further provided is a new use of darusentan in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy, wherein the composition is administered adjunctively with at least one diuretic and at least one antihypertensive drug selected from ACE inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers and calcium channel blockers.
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- Method for treating resistant hypertension
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A method is provided for lowering blood pressure in a patient having clinically diagnosed resistant hypertension. The method comprises administering darusentan to the patient adjunctively with a baseline antihypertensive regimen that comprises administration of at least one diuretic and at least two antihypertensive drugs selected from at least two of (a) ACE inhibitors and angiotensin II receptor blockers, (b) beta-adrenergic receptor blockers and (c) calcium channel blockers. The darusentan is orally administered at a dose and frequency effective, in combination with the baseline regimen, to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures.
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- USE OF SUBSTITUTED 2 PHENYLBENZIMIDAZOLES AS MEDICAMENTS
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The present invention relates to the use of a substituted 2-phenylbenzimidazole of formula I wherein R1, R2, R3, R 4, R5 and m have the meanings given in the claims, for the preparation of a medicament for the treatment or prevention of diseases involving glucagon receptors, as well as new compounds of formula I wherein R1 is a group of formula
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- Total synthesis of optically active m-phenylene PGl2 derivative: Beraprost
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The optical isomers of m-phenylene PGl2 derivative, Beraprost, were synthesized in practical scales from optically active carboxy- cyclopenta[b]benzofurans (12 and 13) by Wittig and Wadsworth reactions as key reactions via the intermediate diols (16a and 16b).
- Wakita, Hisanori,Yoshiwara, Hideo,Nishiyama, Hisao,Nagase, Hiroshi
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p. 1085 - 1110
(2007/10/03)
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- Synthesis of 5,6,7-trinor-4,8-inter-m-phenylene PGI2 and Beraprost
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We have disclosed a new class of stable PGI2 analogue, 5,6,7-trinor- 4,8-inter-m-phenylene PGI2 which has a phenyl ether moiety instead of enol- ether skeleton in PGI2. The m-phenylene PGI2 and its derivative (Betaprost) were synthesized via dihydrocyclopenta[b]benzofuran derivatives as key intermediates by ortho-selective metal-halogen exchange reaction with Grignard reagents and subsequent copper-catalyzed cyclization. The ω-side chains were introduced by stereoselective epoxide formation or Prins reaction.
- Wakita, Hisanori,Matsumoto, Kazuhisa,Yoshiwara, Hideo,Hosono, Yutaka,Hayashi, Ryoji,Nishiyama, Hisao,Nagase, Hiroshi
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p. 2449 - 2474
(2007/10/03)
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