475084-96-9Relevant academic research and scientific papers
Preparation method of medical intermediate
-
Paragraph 0020-0025, (2021/10/11)
The invention provides a preparation method of a medical intermediate 2 - {4 - [(5, 6 - diphenylpyrazine -2 -yl) (propane -2 -yl) amino] butoxy} acetate. The crystallization method uses a mixed solvent composed of a hydrocarbon and an alcohol, the hydroca
METHOD FOR PREPARING PROSTACYCLIN RECEPTOR AGONIST
-
, (2018/03/01)
The present invention relates to preparation methods of a prostacyclin receptor agonist of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide and its intermediates. These methods are simple and convenient to operate, environment-friendly and suitable for industrial production to obtain the product with good yield and high purity.
POLYMORPHIC FORMS AND AMORPHOUS SOLID DISPERSION OF SELEXIPAG
-
Page/Page column 37; 38, (2018/02/28)
The present disclosure relates to crystalline forms of selexipag and their processes for preparation. The present disclosure also relates to an amorphous solid dispersion of selexipag and its processes for their preparation as well as premix of crystalline selexipag and their process.
High-purity match le xipa (by machine translation)
-
, (2017/12/14)
The invention discloses a high-purity match le xipa. By the match le xipa key intermediate 2 - (4 - ((5, 6 - diphenyl pyrazine - 2 - yl) isopropyl amino) butoxy) acetic acid in the organic solvent with the CDI, a sulfonamide in the organic base under the conditions of the reaction. The reaction operation is simple, low cost, environment-friendly, yield>95%, it is suitable for industrial production, the purity of the prepared match le xipa ≥ 99.9%, can better meet the requirements of drug production. The invention prepared match le xipa high purity, thereby facilitating the subsequent more high-quality drugs. (by machine translation)
Preparation method for therapeutic drug selexipag for treating pulmonary arterial hypertension of adults
-
, (2017/08/31)
The invention discloses a preparation method for therapeutic drug selexipag for treating pulmonary arterial hypertension of adults. The therapeutic drug selexipag for treating pulmonary arterial hypertension of adults is prepared through 5-step reaction of starting materials 5-chlorine-2 and 3-diphenyl pyrazine. The invention aims to overcome the defect of higher cost of the present method, shorten the preparation process and provide the preparation method for the therapeutic drug selexipag for treating pulmonary arterial hypertension of adults that is mild in reaction, easy in operation and high in chiral purity.
PROCESS FOR THE PREPARATION OF SELEXIPAG AND INTERMEDIATES THEREOF
-
, (2017/03/28)
The present invention provides processes for the preparation of Selexipag compound of formula (1). The present invention also provides processes for the preparation of 4-[(5,6-diphenyl-pyrazin-2-yl)-isopropyl -amino]-butan-1-ol (2), and 4-isopropylamino-butan-1-ol of formula (3), which are intermediates for the synthesis of Selexipag (1 ).
AN IMRPOVED PROCESS FOR THE PREPARATION OF SELEXIPAG OR ITS PHARMACEUTICALLY ACCEPTABLE SALTS
-
, (2017/08/01)
The present invention provides an improved process for Selexipag of formula (I) or its pharmaceutically acceptable salts.
PROCESS FOR THE PREPARATION OF DIPHENYLPYRAZINE DERIVATIVES
-
Page/Page column 12, (2017/10/31)
The present invention relates to a process for the preparation of amorphous Selexipag from Selexipag crystalline salts using a solvent.
Selexipag: An Oral and Selective IP Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension
Asaki, Tetsuo,Kuwano, Keiichi,Morrison, Keith,Gatfield, John,Hamamoto, Taisuke,Clozel, Martine
, p. 7128 - 7137 (2015/10/05)
Prostacyclin controls cardiovascular function via activation of the prostacyclin receptor. Decreased prostacyclin production occurs in several cardiovascular diseases. However, the clinical use of prostacyclin and its analogues is complicated by their chemical and metabolic instability. A medicinal chemistry program searched for novel nonprostanoid prostacyclin receptor agonists not subject to these limitations. A compound with a diphenylpyrazine structural core was synthesized. Metabolic stability and agonist potency were optimized through modification of the linear side chain. Compound 12b (MRE-269, ACT-333679) was identified as a potent and highly selective prostacyclin receptor agonist. Replacement of the terminal carboxyl group with an N-acylsulfonamide group yielded parent compound 26a (selexipag, NS-304, ACT-293987), which is orally active and provides sustained plasma exposure of 12b. Compound 26a was developed for the treatment of pulmonary arterial hypertension and shown to reduce the risk of the composite morbidity/mortality end point in a phase 3 event-driven clinical trial.
Structure-activity studies on diphenylpyrazine derivatives: A novel class of prostacyclin receptor agonists
Asaki, Tetsuo,Hamamoto, Taisuke,Sugiyama, Yukiteru,Kuwano, Keiichi,Kuwabara, Kenji
, p. 6692 - 6704 (2008/03/27)
To develop nonprostanoid prostacyclin receptor agonists with a high degree of metabolic resistance and an extended duration of action, a novel series of diphenylpyrazine derivatives was synthesized and evaluated for their inhibition of ADP-induced human platelet aggregation. Structure-activity relationship studies on the side chain containing the carboxylic acid moiety of the lead compound 5c showed that the length of the linker and the presence of the concatenating nitrogen atom adjacent to the pyrazine ring are critical for the antiaggregatory activity. This study led to the discovery of 2-amino-5,6-diphenylpyrazine derivatives 8c, 15a, and 15b, which showed potent inhibition of platelet aggregation with IC50 values of 0.2 μM. Among these compounds, 15b is an orally available and long-lasting prostacyclin receptor agonist which is promising for the treatment of various vascular diseases.
