475084-97-0

Basic information

• Product Name: 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-cyclopentylamino]butyloxy}acetic acid tert-butyl ester
• CAS NO: 475084-97-0
• Molecular Weight: 501.669
• Mol File: 475084-97-0.mol

Chemical Properties

• CAS DataBase Reference: 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-cyclopentylamino]butyloxy}acetic acid tert-butyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-cyclopentylamino]butyloxy}acetic acid tert-butyl ester(475084-97-0)
• EPA Substance Registry System: 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-cyclopentylamino]butyloxy}acetic acid tert-butyl ester(475084-97-0)

Safety Data

• Hazardous Substances Data: 475084-97-0(Hazardous Substances Data)

Upstream product

• 120-92-3 cyclopentanone 
• 5292-43-3 bromoacetic acid tert-butyl ester 

Relevant articles and documents

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.

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.

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.