- Synthesis method of riociguat
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The invention relates to the field of drug synthesis, in particular to a preparation method of riociguat. The preparation method comprises the steps that a compound 3 is taken as a raw material and is reacted with methyl chloroformate to obtain a hydrochloride of a compound 2, and the hydrochloride of the intermediate 2 is reacted with a methylation reagent under base catalysis to obtain riociguat. In the synthesis of the compound 2, pyridine used as a solvent and alkali is avoided; in the synthesis of the compound 1, the use of unsafe and expensive reagents such as NaH and LiHMDS is avoided. The riociguat synthesis method provided by the invention has the advantages of simplicity and convenience in operation, mild conditions, environmental friendliness, high total yield and purity, low cost and the like, and is suitable for large-scale industrial production.
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Paragraph 0033-0034; 0037-0040; 0041; 0044-0047
(2021/09/04)
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- PROCESS FOR THE PREPARATION OF METHYL 4,6-DIAMINO-2-[1-(2-FLUOROBENZYL)-1H-PYRAZOLO[3,4-B]PYRIDIN-3-YL]-5-PYRIMIDINYL(METHYL)CARBAMATE AND ITS POLYMORPHS THEREOF
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The present invention relates to an improved process for the preparation of methyl 4,6-diamino-2-[ 1-(2-fluorobenzyl)-1 H -pyrazolo[3,4-b )pyridin-3 -yl]-5-pyrimidinyl(methyl)carbamatecompound of formula-1 and its polymorphs thereof, represented by the fo
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- Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure
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The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure-Activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound 24, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported.
- Follmann, Markus,Ackerstaff, Jens,Redlich, Gorden,Wunder, Frank,Lang, Dieter,Kern, Armin,Fey, Peter,Griebenow, Nils,Kroh, Walter,Becker-Pelster, Eva-Maria,Kretschmer, Axel,Geiss, Volker,Li, Volkhart,Straub, Alexander,Mittendorf, Joachim,Jautelat, Rolf,Schirok, Hartmut,Schlemmer, Karl-Heinz,Lustig, Klemens,Gerisch, Michael,Knorr, Andreas,Tinel, Hanna,Mondritzki, Thomas,Trübel, Hubert,Sandner, Peter,Stasch, Johannes-Peter
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p. 5146 - 5161
(2017/06/28)
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- PROCESS FOR THE PREPARATION OF METHYL 4,6-DIAMINO-2-[L-(2-FHIOROBENZVR)-LH-PYRAZOLO I3,4-BLPVRIDIN-3-VN-5-PYRIMIDINYL(METHVL)CARBAMATE AND ITS POLYMORPHS THEREOF
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The present invention relates to process for the preparation of methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-lH-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl(methyl)carbamate and its polymorphs thereof compound of formula-1, represented by the following structur
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- Preparation method of riociguat
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The invention relates to the field of medicinal chemistry, in particular to a preparation method of riociguat. According to the method, a compound of a formula 2 serves as a raw material, and reaction is conducted in a solvent under the existence of a met
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Paragraph 0020; 0021; 0022; 0023; 0024; 0025; 0026-0040
(2017/08/29)
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- The preparation method of the west leo gua (by machine translation)
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The invention discloses a method for preparation of west leo gua, its to 1 - (2 - fluorobenzyl) - 1 H - pyrazolo [3, 4 - b] pyridine - 3 - carboxamidine hydrochloride as the raw material, via the four-step reaction 2 - [1 - (2 - fluorobenzyl) - 1 H - pyra
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Paragraph 0086; 0087; 0088; 0092; 0093
(2017/10/05)
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- A compound intermediate [...] and its as the application of the (by machine translation)
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This invention relates to a kind of compound, can be used as intermediate [...] and its derivatives. Also disclosed are intermediates to a new method of preparing [...], [...] and the purity of the obtained high, effectively reducing the occurrence of the side reaction, the production cost is saved. (by machine translation)
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Paragraph 0083; 0084; 0085; 0086
(2016/10/09)
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- Preparation method of riociguat
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The invention discloses a preparation method of riociguat. The preparation method comprises the steps of firstly, taking 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-formamidine hydrochloride and 2-aminopropanediamide as basic raw materials, adding str
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- Compound and application thereof in preparation of riociguat
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The present invention discloses compound 5-methylamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo [3,4-b] pyridin-3-yl] pyrimidine-4,6-diamine, which can be used as an intermediate of riociguat and riociguat derivatives. The present invention also discloses a new method for the preparation of the riociguat by use of the intermediate, and the obtained riociguat has high yield and purity, the occurrence of side effects can be effectively reduced, and production cost is saved.
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- A method for synthesizing [...]
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The invention relates to a method for synthesizing riociguat. The method includes the following steps: 1, a compound 1-(2-fluorobenzyl)-1H-[3,4-b] pyridine derivative-3-formamidine hydrochloride (1) and a compound benzeneazomalononitrile (2) are reacted i
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Paragraph 0034
(2017/03/28)
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- Riociguat preparation method
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The present invention discloses a new riociguat preparation method comprising the following steps: preparing intermediate N-substituted-benzyl-N-methyl-2-amino malononitrile shown in the structural formula V, preparing 5-(N-methyl) (R-substituted) benzyl amino-2-[1-(2-fluorobenzyl)-1 H-pyrazole [3, 4-b] pyridine-3-yl] pyrimidine-4, 6-diamine shown in the structural formula III, preparing 5-methyl amino-2-[1-(2-fluorobenzyl)-1 H-pyrazole [3, 4-b] pyridine-3-yl] pyrimidine-4, 6-diamine shown in the structural formula II, and preparing riociguat shown in the structural formula I. The obtained riociguat has high yield and purity, the occurrence of side effects can be effectively reduced, and production cost is saved.
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Paragraph 0082; 0099; 0100; 0101
(2017/01/26)
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- Preparation method and application of pyrazolo[3, 4-b]pyridine compound intermediate
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The invention provides a preparation method and application of a pyrazolo[3, 4-b]pyridine compound intermediate. Specifically, the intermediate structure is shown as formula IV, wherein the groups are defined as the specification and claims. The intermedi
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- PROCESS FOR PREPARING METHYL METHYLCARBAMATE AND ITS PURIFICATION FOR USE AS PHARMACEUTICALLY ACTIVE COMPOUND
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The present invention relates to a process for preparing methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamate of the formula (I) and to a process for purifying the crude product of the compound of the for
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- Novel Combination Containing a Stimulator of Soluble Guanylate Cyclase and a Lipid-Lowering Substance
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A combination product which comprises as pharmaceutically active ingredients at least one active ingredient component A and at least one active ingredient component B, where active ingredient component A is a direct soluble guanylate cyclase stimulator of
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Page/Page column 14
(2010/11/28)
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