313348-27-5

Basic information

• Product Name: REGADENOSON
• Synonyms: REGADENOSON;2-[4-[(Methylamino)carbonyl]-1H-pyrazol-1-yl]-adenosin;2-[4-[(Methylamino)carbonyl]-1H-pyrazol-1-yl]-adenosine;Regadenoson(CVT-3146);6-Amino-2-[4-(methylcarbamoyl)-1H-pyrazol-1-yl]purine-9-yl-beta-D-ribofuranoside;6-Amino-2-[4-(methylcarbamoyl)-1H-pyrazol-1-yl]purine-9-yl-beta-D-ribofuranoside Regadenoson;Regadenoson 6-Amino-2-[4-(methylcarbamoyl)-1H-pyrazol-1-yl]purine-9-yl-beta-D-ribofuranoside;1-(6-Amino-9-((2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-9H-purin-2-yl)-N-methyl-1H-pyrazole-4-carboxamide monohydrate
• CAS NO: 313348-27-5
• Molecular Formula: C15H18N8O5
• Molecular Weight: 390.35402
• Product Categories: Nucleotides and Nucleosides;Bases & Related Reagents;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals;Inhibitors
• Mol File: 313348-27-5.mol
• Article Data: 19

Chemical Properties

• Melting Point: 158-160°C
• Appearance: Off-white solid
• Density: 1.98 g/cm³
• Refractive Index: 1.896
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly, Sonicated)
• PKA: 13.07±0.70(Predicted)
• CAS DataBase Reference: REGADENOSON(CAS DataBase Reference)
• NIST Chemistry Reference: REGADENOSON(313348-27-5)
• EPA Substance Registry System: REGADENOSON(313348-27-5)

Safety Data

• Hazardous Substances Data: 313348-27-5(Hazardous Substances Data)

Usage

Description

Lexiscan ?(regadenoson) is an injectable adenosine A2A receptor agonist for use as a pharmacologic stress agent in myocardial perfusion imaging (MPI) studies in patients unable to undergo adequate exercise induced stress. Regadenoson is the first adenosine A2A receptor agonist shown to be safe and effective as a pharmacologic stress agent in MPI studies. It is delivered as a rapid bolus (approximately 10 seconds) with no dose adjustment required for body weight. The product was developed under a license and collaboration agreement between CV Therapeutics and Astellas, and was launched by Astellas in June of 2008.

Chemical Properties

Off-White Solid

Uses

Different sources of media describe the Uses of 313348-27-5 differently. You can refer to the following data:
1. A selective A2A adenosine receptor agonist in myocardial imaging
2. Regadenoson is a selective, short-acting adenosine A2A receptor agonist (Ki = 1.1 nM for pig striatum A2A receptor). It increases coronary blood flow 3.4- to 3.8-fold with a half-time to reversal of 1.9-2.6 minutes in open-chest anesthetized pigs. Regadenoson is used to induce hyperemia (increased blood flow), particularly in the context of myocardial perfusion imaging. It has also been found to increase the delivery of compounds to the central nervous system through the blood-brain barrier in animals.
3. Regadenoson is a selective and potent A2A adenosine receptor agonist (1). The adenosine A2A receptor is a G-protein-coupled receptor and a key therapeutic target for oncologic, inflammatory, Parkinson''s and cardiovascular diseases (2). In rodent studies, it has been shown that co-administration of Regadenoson with Temozolomide (T017775) can increase Temozolomide concentration in the brain (3).

Synthesis

The synthesis of regadenoson has been reported in several papers and patents and a scalable procedure is detailed in the scheme. The synthesis was initiated with the reaction of 2- chloroadenosine hemihydrate (94) and hydrazine monohydrate at 40-50 °C to provide 95 in 81% yield with 99.3% purity. Hydrazine 95 was condensed with ethyl-2-formyl-3- oxopropionate (96) under refluxing IPA to furnish the pyrazole 97 in 77% yield which was collected by filtration and used in next step without further purification. Pyrazole 97 was then reacted with methyl amine at room temperature to provide regadenoson (XV). Although the yield was not reported, the product was collected by simple filtration.

in vitro

regadenoson was selective for the a2a adenosine receptor versus the a1, a2b, and a3 receptors in binding and functional studies. regadenoson was also found to be a full and potent agonist to cause coronary vasodilation, a response that has a very large a2a receptor reserve [1].

in vivo

in a study of 10 conscious dogs, authors compared intravenously injected regadenoson to that of adenosine. regadenoson caused a dose-dependent increase of coronary blood flow (cbf), whereas adenosine was less potent but produced equivalent hyperemia. thus, authors concluded that regadenoson is a potent coronary vasodilator with a short duration of action, minimal and transient systemic hemodynamic effects, and ease of administration [1].

references

[1] cerqueira md. the future of pharmacologic stress: selective a2a adenosine receptor agonists. am j cardiol. 2004 jul 22;94(2a):33d-40d; discussion 40d-42d.

InChI:InChI=1/C15H18N8O5/c1-17-13(27)6-2-19-23(3-6)15-20-11(16)8-12(21-15)22(5-18-8)14-10(26)9(25)7(4-24)28-14/h2-3,5,7,9-10,14,24-26H,4H2,1H3,(H,17,27)(H2,16,20,21)/t7-,9-,10-,14-/m1/s1

Upstream product

• 74-89-5 methylamine 
• 313348-16-2 CVT 3127 
• 24639-06-3 ((3aR,4R,6R,6aR)-6-(6-amino-2-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol 
• 1154383-52-4 N-methyl-1H-pyrazole-4-carboxamide 
• 146-77-0 2-Chloroadenosine 
• 35109-88-7 2-iodoadenosine 
• 1423073-21-5 2-(4-methoxycarbonylpyrazol-1-yl)adenosine 
• 146-78-1 2-fluoroadenosine 
• 15763-11-8 2-hydrazinoadenosine 

Relevant articles and documents

Preparation method of A2A adenosine receptor agonist

The invention discloses a preparation method of an A2A adenosine receptor agonist. The preparation method comprises the following steps of: (1) reacting 2-chloroadenosine with acetic anhydride by taking sodium acetate as a catalyst to prepare a compound shown in a formula (1); (2) reacting the compound shown in the formula (1) with hydrazine hydrate by taking methanol as a reaction medium to prepare a compound shown in a formula (2); (3) reacting the compound shown in the formula (2) with 2-formyl-3-oxoethyl propionate to prepare a compound shown in a formula (3); and (4) reacting the compound shown in the formula (3) with a methylamine water solution to prepare the A2A adenosine receptor agonist. According to the preparation method, the 2-chloroadenosine is taken as a starting raw material, and hydroxyl and amino are protected by using an AC protecting group, so that formation of relevant impurities is avoided effectively; and the dosage of a genotoxic reagent hydrazine hydrate is reduced greatly, excessive 2-formyl-3-oxoethyl propionate reacts with the compound shown in the genotoxic warning structural formula (2), the residue of the compound shown in the formula (2) is controlled at a very low level, and a relatively high-purity Regabardine product is obtained finally.

NOVEL POLYMORPH OF REGADENOSON AND PROCESS FOR PREPARATION THEREOF

Processes are provided for the preparation of a stable polymorphic form C of regadenoson, the process involving steps of a) obtaining a solution of regadenoson in benzyl alcohol solvent, b) maintaining the reaction mixture of step a) to about 10° C. to about 90° C., and c) isolating the stable polymorphic form C of regadenoson. Polymorphic form C may be characterized by an x-ray powder diffraction pattern with peaks at about 6.1, 10.2, 10.6, 19.0 and 25.4.±0.2 degrees 2-theta.

Sweden deshong new intermediate and its preparation method and application

The invention relates to new regadenoson intermediates, a preparation method and an application thereof, and a preparation method for preparing regadenoson with the intermediates. The invention discloses the new regadenoson intermediate represented as the general formula I, a method for preparing the intermediate with hydrazinoadenine, and also a method for preparing regadenoson, wherein the method for preparing regadenoson includes steps of preparing a compound represented as the formula III with the intermediate represented as the general formula I and a compound represented as the general formula II under a catalyst, and then converting the compound represented as the formula III into the regadenoson. The method is simple in operations, is high in yield, is low in cost and is very suitable for industrialized production.