cas 475086-01-2, NS-304 | Articles data

Articles about 475086-01-2Total 20 be found

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Synthesis method of diphenyl pyrazine derivative
The invention discloses a synthesis method of a diphenyl pyrazine derivative. The method is characterized in that benzil and glycinamide are used as raw materials, and a target product is prepared through five-step reaction. The obtained target product is high in purity, subsequent production of high-quality drugs is facilitated, and the synthesis method is reasonable in route design, mild in reaction condition, free of high-temperature reaction, good in safety and high in feasibility.
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(2021/06/13)

Preparation method of medical intermediate
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
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(2021/10/11)

Preparation method for Selexipag intermediate
The invention provides a method for preparing a Selexipag intermediate 4-((5,6-diphenyl-2-pyrazinyl)(1-methylethyl)amino)-1-butanol. The method includes protecting 4-isopropylamino n-butyl alcohol byusing a hydroxy protecting group reagent, performs addition with 5,6-diphenyl-2-pyrazinyl trifluoromethanesulfonate, and obtains a target compound by removing protecting groups. The preparation methodis high in yield, low in production cost, mild in condition, simple in operation and suitable for industrial production.
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(2019/03/15)

Match le xipa intermediate and match le xipa preparation method (by machine translation)
The invention discloses a match le xipa intermediate and match le xipa preparation method, the midbody is compound And compounds The present invention provides a preparation method of match le xipa of reasonable process design, is suitable for industrial scale production. (by machine translation)
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(2018/10/19)

METHOD FOR PREPARING PROSTACYCLIN RECEPTOR AGONIST
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.
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(2018/03/01)

CRYSTALLINE FORM VI OF SELEXIPAG
The present disclosure relates to solid state forms of Selexipag, processes for preparation thereof and pharmaceutical compositions thereof.
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Paragraph 00142-00144

(2018/02/28)

POLYMORPHIC FORMS AND AMORPHOUS SOLID DISPERSION OF SELEXIPAG
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.
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(2018/02/28)

Preparation method of selexipag
The invention discloses a preparation method of selexipag. The method comprises the following steps that a compound II and 2-halogenated acetamide are subjected to condensation reaction in an alkalinecondition, so as to obtain a compound I, and then the c
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Paragraph 0026; 0030; 0031

(2018/11/03)

Preparation method for therapeutic drug selexipag for treating pulmonary arterial hypertension of adults
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.
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(2017/08/31)

PROCESS FOR THE PREPARATION OF DIPHENYLPYRAZINE DERIVATIVES
The present invention relates to a process for the preparation of amorphous Selexipag from Selexipag crystalline salts using a solvent.
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Page/Page column 14

(2017/10/31)

PROCESS FOR THE PREPARATION OF SELEXIPAG AND INTERMEDIATES THEREOF
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 ).
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(2017/03/28)

PROCESSES FOR PREPARATION OF SELEXIPAG AND ITS AMORPHOUS FORM
The present application relates to processes for preparation of Selexipag, its amorphous form, amorphous solid dispersion and pharmaceutical composition thereof. Formula (I):
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Page/Page column 20; 21

(2017/03/14)

SOLID STATE FORMS OF SELEXIPAG
The present disclosure relates to solid state forms of Selexipag, in particular selexipag forms IV and V, and processes for preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
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Paragraph 0097-0098

(2017/03/21)

AN IMRPOVED PROCESS FOR THE PREPARATION OF SELEXIPAG OR ITS PHARMACEUTICALLY ACCEPTABLE SALTS
The present invention provides an improved process for Selexipag of formula (I) or its pharmaceutically acceptable salts.
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(2017/08/01)

High-purity match le xipa (by machine translation)
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)
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(2017/12/14)

Synthetic method of selexipag
The invention discloses a synthetic method of selexipag. According to the method, 4-[(t-butyloxycarboryl)(isopropyl) amino]-1-butanol and tert-butyl bromoacetate are subjected to a condensation reaction, and obtained 4-[(t-butyloxycarboryl)(isopropyl) amino butoxyl] tert-butyl acetate is subjected to a hydrolysis reaction under an alkaline reaction; obtained 4-[(t-butyloxycarboryl)(isopropyl) amino butoxyl] acetic acid and methanesulfonamide are subjected to a condensation reaction; obtained 2-[4-[(t-butyloxycarboryl)(isopropyl) amino butoxyl]-N-(methylsulfonyl) acetamide is subjected to a deprotection reaction under an acid condition, obtained 2-[4-(isopropyl) amino butoxyl]-N-(methylsulfonyl) acetamide and 5-chloro-2,3-diphenyl pyrazine are subjected to a substitution reaction, and the finished product selexipag is obtained. The method has a reasonable and concise process route and is environment-friendly and suitable for industrial production, the operation is simplified, and the cost is relatively low.
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(2018/02/04)

Preparation method of selexipag
The invention discloses a preparation method of selexipag, and relates to the technical field of preparation of drugs for treating pulmonary hypertension. The preparation method comprises the following steps: adding a compound as shown in the formula I and a compound as shown in the formula II in an organic solvent; adding alkali; stirring at the reaction temperature of 10-40 DEG C and carrying out Williamson reaction; synthesizing a compound as shown in the formula A, namely the selexipag. The organic solvent is 1-4-dioxane; the alkali is sodium tert-butoxide, potassium tert-butoxide or mixed alkalis of sodium tert-butoxide and potassium tert-butoxide. A synthetic route is reasonable in design, reaction conditions are mild, the cost is low, special equipment is not required, a product is high in purity and high in yield, and aftertreatment is simple and convenient, so that the preparation method of the selexipag is suitable for industrial production.
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Paragraph 0023

(2016/12/16)

Selexipag: An Oral and Selective IP Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension
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.
Asaki, Tetsuo,Kuwano, Keiichi,Morrison, Keith,Gatfield, John,Hamamoto, Taisuke,Clozel, Martine
p. 7128 - 7137
(2015/10/05)

Structure-activity studies on diphenylpyrazine derivatives: A novel class of prostacyclin receptor agonists
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.
Asaki, Tetsuo,Hamamoto, Taisuke,Sugiyama, Yukiteru,Kuwano, Keiichi,Kuwabara, Kenji
p. 6692 - 6704
(2008/03/27)

HETEROCYCLIC COMPOUND DERIVATIVES AND MEDICINES
The present invention provides a compound which is useful as a PGI2 receptor agonist, and a pharmaceutical composition. The present invention is directed to a pharmaceutical composition comprising a compound represented by the following formula [1]: (R1 and R2 are the same or different and each represents optionally substituted aryl, Y represents N or CH, Z represents N or CH, A represents NH, NR5, O, S, or ethylene, R5 represents alkyl, D represents alkylene or alkenylene, E represents phenylene or single bond, G represents O, S, or CH2, R3 and R4 are the same or different and each represents hydrogen or alkyl, Q represents carboxy, alkoxycarbonyl, tetrazolyl, carbamoyl, or N-(alkylsulfonyl)carbamoyl), or a pharmaceutically acceptable salt thereof as an active ingredient.
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Page 53-54

(2010/02/05)