148849-67-6 Usage
Description
Ivabradine hydrochloride, also known as Procoralan, is a white to off-white solid that is a hydrochloride obtained by combining ivabradine with one molar equivalent of hydrochloric acid. It is a specific inhibitor of the If current, which is the primary pacemaking current in the sinoatrial (SA) node of the heart. By interacting with f-channels on the intracellular side of the plasma membrane, ivabradine hydrochloride reduces the speed of diastolic depolarization and decreases heart rate.
Uses
Used in Angina Therapeutic Applications:
Ivabradine hydrochloride is used as a heart rate-lowering agent for the treatment of chronic stable angina. It acts specifically on the pacemaker activity of the sinoatrial node, providing a viable alternative to patients with contraindications or intolerance of beta-blockers.
Used in Antianginal Applications:
Ivabradine hydrochloride is used as a selective bradycardic agent with a direct effect on the pacemaker If current of the sinoatrial node. It helps in the treatment of angina by reducing the heart rate, which in turn decreases the oxygen demand of the heart and alleviates the symptoms of angina.
Used in Cardiology:
Ivabradine hydrochloride is used as a potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel (HCN) blocker in embryoid body (EB) and rat engineered heart tissue (EHT). This application aids in the study and understanding of the role of If current in the regulation of heart rate and its potential implications in the development of new treatments for cardiovascular diseases.
Used in Drug Development:
Ivabradine hydrochloride is used in the development of new heart-rate reducing compounds that act specifically on the sinoatrial (SA) node. These bradycardic agents are explored as an alternative to traditional b-adrenergic blockers and calcium channel blockers, which may have unwanted negative inotropic and hypotensive effects.
Originator
Servier (France)
Biochem/physiol Actions
Ivabradine is used to treat chronic heart failure.
Clinical Use
Symptomatic treatment of chronic stable angina pectoris
in patients with sinus rhythm
Treatment of mild to severe chronic heart failure
Drug interactions
Potentially hazardous interactions with other drugs
Anti-arrhythmics: increased risk of ventricular
arrhythmias with amiodarone and disopyramide.
Antibacterials: concentration possibly increased by
clarithromycin and telithromycin - avoid; increased
risk of ventricular arrhythmias with erythromycin -
avoid.
Antifungals: concentration increased by ketoconazole
- avoid; concentration increased by fluconazole -
reduce initial ivabradine dose; concentration possibly
increased by itraconazole - avoid.
Antimalarials: increased risk of ventricular
arrhythmias with mefloquine.
Antipsychotics: increased risk of ventricular
arrhythmias with pimozide.
Antivirals: concentration possibly increased by
ritonavir - avoid.
Beta-blockers: increased risk of ventricular
arrhythmias with sotalol.
Calcium-channel blockers: concentration increased
by diltiazem and verapamil - avoid.
Grapefruit juice: ivabradine concentration increased.
Pentamidine: increased risk of ventricular
arrhythmias.
St John’s wort: ivabradine concentration reduced -
avoid.
Metabolism
Ivabradine is extensively metabolised by the liver
and the gut by oxidation through cytochrome P450
3A4 (CYP3A4) only. The major active metabolite is
N-desmethyl-ivabradine (S 18982) with an exposure
about 40% of that of the parent compound. This active
metabolite undergoes further metabolism by CYP3A4.
Excretion of metabolites occurs to a similar extent via
faeces and urine.
Check Digit Verification of cas no
The CAS Registry Mumber 148849-67-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,4,8,8,4 and 9 respectively; the second part has 2 digits, 6 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 148849-67:
(8*1)+(7*4)+(6*8)+(5*8)+(4*4)+(3*9)+(2*6)+(1*7)=186
186 % 10 = 6
So 148849-67-6 is a valid CAS Registry Number.
InChI:InChI=1/C27H36N2O5.ClH/c1-28(17-21-11-20-14-25(33-4)26(34-5)16-22(20)21)8-6-9-29-10-7-18-12-23(31-2)24(32-3)13-19(18)15-27(29)30;/h12-14,16,21H,6-11,15,17H2,1-5H3;1H/t21-;/m1./s1
148849-67-6Relevant articles and documents
AN IMPROVED PROCESS FOR THE SYNTHESIS OF IVABRADINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
-
, (2019/11/12)
: Disclosed herein is an improved process for the preparation of Ivabradine and pharmaceutically acceptable salts thereof. The invention more particularly disclosesthe synthesis of key intermediates viz.,(S)-N-[(4,5-dimethoxybenzocydobut-l-yl)-methyl]-N- (methyl)amine hydrochloride of Formula-II and 3-(3-Iodopropyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzapin-2-one of Formula-III, and its use in industrial synthesis of Ivabradine and pharmaceutically acceptable salts thereof.
(1 S) - 4, 5 - dimethoxy - 1 - [(methylamino) methyl] benzocyclobutane preparation of hydrochloride salts of method
-
, (2018/04/02)
The invention provides a preparation method of (1S)-4,5-dimethoxy-1-[(methylamino)methyl]benzocyclobutane hydrochloride, which specially comprises the following step: carrying out reduction and salting-out on 4,5-dimethoxybenzocyclobutyl-1-methyl formamide in an inert solvent to finally obtain the (1S)-4,5-dimethoxy-1-[(methylamino)methyl]benzocyclobutane hydrochloride (I). The reaction is simple to operate, has the advantages of mild reaction conditions, clean and accessible raw/auxiliary materials, low overall cost, high chemical and enantiomer purity and the like, and therefore, is suitable for industrial production.
Exploiting the Biocatalytic Toolbox for the Asymmetric Synthesis of the Heart-Rate Reducing Agent Ivabradine
Pedragosa-Moreau, Sandrine,Le Flohic, Alexandre,Thienpondt, Vivien,Lefoulon, Fran?ois,Petit, Anne-Marie,Ríos-Lombardía, Nicolás,Morís, Francisco,González-Sabín, Javier
supporting information, p. 485 - 493 (2017/02/10)
Several chemoenzymatic routes have been evaluated for the production of the heart-rate reducing agent ivabradine. Lipases and ω-transaminases have been identified as useful biocatalysts for the preparation of key enantiopure precursors. The lipase-catalysed kinetic resolution by alkoxycarbonylation of a racemic primary amine and subsequent chemical reduction of the resulting carbamate provided an N-methylated (S)-amine, one step away from ivabradine. Alternatively, the dynamic kinetic resolution by asymmetric bioamination of an aldehyde precursor enabled, in a four-step sequence, the preparative scale synthesis of enantiopure ivabradine in 50% overall yield. (Figure presented.).