- PROCESS FOR THE PREPARATION OF AN ENDOTHELIN RECEPTOR ANTAGONIST
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The present invention relates to a novel process for the preparation of a compound of formula (I) wherein R is a methyl or methoxy group; to certain novel intermediates prepared in such a process and their use.
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Page/Page column 20-21
(2013/05/09)
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- Improved Process For The Preparation Of Endothelin Receptor Antagonists
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The present invention relates to improved processes for the preparation of Endothelin receptor antagonists, their salts and intermediates.
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Page/Page column 8
(2011/11/06)
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- Kinetic resolution of racemic α-tert-alkyl-α-hydroxy esters by enantiomer-selective carbamoylation
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Kinetic resolution of sterically hindered racemic α-tert-alkyl- α-hydroxy esters is performed by enantiomer-selective carbamoylation with the t-Bu-Box-Cu(II) catalyst (Box = bis-(oxazoline)). The reaction with 0.5 equiv of n-C3H7NCO is carried out with a substrate-to-catalyst molar ratio of 500-5000 at -20 to 25 °C. The high enantiomer-discrimination ability of the catalyst achieves an excellent stereoselectivity factor (s = kfast/kslow) of 261 in the best case. A catalytic cycle for this reaction is proposed (Figure presented).
- Kurono, Nobuhito,Ohtsuga, Kentaro,Wakabayashi, Masanori,Kondo, Tadahiro,Ooka, Hirohito,Ohkuma, Takeshi
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experimental part
p. 10312 - 10318
(2012/01/30)
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- IMPROVED PROCESS FOR THE PREPARATION OF ENDOTHELIN RECEPTOR ANTAGONISTS
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The present invention relates to improved processes for the preparation of Endothelin receptor antagonists, their salts and intermediates.
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Page/Page column 20
(2010/08/05)
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- Azinyloxy, and phenoxy-diaryl-carboxylic acid derivatives, their preparation and use as mixed ETA/ETB endothelin receptor antagonists
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The invention relates to carboxylic acid derivatives of the formula I where the radicals have the meanings stated in the description, and to their use as drugs.
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Page column 16
(2010/02/05)
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- Structural similarity and its surprises: Endothelin receptor antagonists -process research and development report
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Process research and pilot plant processes are described for three endothelin (ET) receptor antagonists. The efficient synthesis of the parent compound Darusentan proceeds via a Darzens reaction from chloroacetate with benzophenone, addition of methanol to the resulting epoxide, saponification of the alkyl propionate and optical resolution of the racemic acid by crystallisation with a chiral amine. The final stage of the synthetic sequence involves the introduction of a pyrimidine moiety. Intermediates formed during this process can be used as starting materials for the synthesis of the two other ET receptor antagonists BSF 420627 and BSF 302146. An ether exchange reaction, which replaces the methoxy with a phenethyloxy substituent, enabled BSF 420627 to be prepared. The synthetic route to BSF 302146 employs trimethylaluminum to methylate the epoxide produced by the Darzens reaction.
- Jansen,Knopp,Amberg,Bernard,Koser,Mueller,Muenster,Pfeiffer,Riechers
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- Discovery and synthesis of (S)-3-[2-(3,4-dimethoxyphenyl)ethoxy]-2(4,6- dimethylpyrimidin-2-yloxy)-3,3-diphenylpropionic acid (LU 302872), a novel orally active mixed ET(A)/ET(B) receptor antagonist
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Structural variation of the endothelin A-selective antagonist (S)-3- methoxy-2-(4,6-dimethoxy-pyrimidin-2-yloxy)-3,3-diphenylpropionic acid (LU 135252) led to analogues which retain ETA affinity but exhibit substantial ET(B) affinity as well. The most active derivative obtained is (S)-3-[2- (3,4-dimethoxyphenyl)ethoxy]-2-(4,6-dimethylpyrimidin-2-yloxy)-3,3- diphenylpropionic acid (LU 302872), which can be prepared in enantiomerically pure form in eight steps via an acid-catalyzed transetherification. It has a K(i) = 2.15 nM for binding to the ETA receptor and a K(i) = 4.75 nM for binding to the ET(B) receptor, is orally available, and antagonizes the big ET-induced blood pressure increase in rats and the big ET-induced bronchospasm in guinea pigs each time at a dose of 10 mg/kg.
- Amberg, Willi,Hergenr?der, Stefan,Hillen, Heinz,Jansen, Rolf,Kettschau, Georg,Kling, Andreas,Klinge, Dagmar,Raschack, Manfred,Riechers, Hartmut,Unger, Liliane
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p. 3026 - 3032
(2007/10/03)
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