104757-53-1

Basic information

• Product Name: Barnidipine
• Synonyms: hydrochloride,(s-(r*,r*))-hyl1-(phenylmethyl)-3-pyrrolidinyleste;ly198561;mepirodipinehydrochloride;ym09730-5;3-((S)-1-Benzylpyrrolidin-3-yl) 5-Methyl 2,6-diMethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride;(4S)-1,4-Dihydro-2,6-diMethyl-4-(3-nitrophenyl)-3,5-Pyridinedicarboxylic Acid 3-Methyl 5-[(3S)-1-(phenylMethyl)-3-pyrrolidinyl] Ester Hydrochloride;[S-(R*,R*)]-1,4-Dihydro-2,6-diMethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic Acid Methyl 1-(PhenylMethyl)-3-pyrrolidinyl Ester Monohydrochloride;Barnidipine Hydrochloride l
• CAS NO: 104757-53-1
• Molecular Formula: C₂₇H₂₉N₃O₆*ClH
• Molecular Weight: 528
• Product Categories: Aromatics;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;API;Heterocycle-Pyridine series
• Mol File: 104757-53-1.mol
• Article Data: 5

Chemical Properties

• Melting Point: 223-226°C
• Boiling Point: 614.5 °C at 760 mmHg
• Flash Point: 325.4 °C
• Appearance: /
• Vapor Pressure: 4.94E-15mmHg at 25°C
• Storage Temp.: Refrigerator
• Solubility: insoluble in H2O; insoluble in EtOH; ≥16.3 mg/mL in DMSO with gentle warming
• CAS DataBase Reference: Barnidipine(CAS DataBase Reference)
• NIST Chemistry Reference: Barnidipine(104757-53-1)
• EPA Substance Registry System: Barnidipine(104757-53-1)

Safety Data

• Hazardous Substances Data: 104757-53-1(Hazardous Substances Data)

Usage

Description

Barnidipine, also known as Barnidipine hydrochloride, is a vasodilating dihydropyridine calcium antagonist with potent hypotensive effects. It is characterized by its pale yellow solid appearance and is commonly marketed under the brand name Hypoca. Barnidipine demonstrates antihypertensive activity by reducing peripheral vascular resistance and has been found to be more potent and longer-acting than other dihydropyridines such as nicardipine, nifedipine, and nitrendipine.

Uses

Used in Pharmaceutical Industry:
Barnidipine is used as an antihypertensive agent for the treatment of hypertension. It is particularly effective in reducing blood pressure in spontaneously hypertensive rats when administered orally at 1 and 3 mg/kg per day. Formulations containing barnidipine have been utilized as a treatment for hypertension, making it a valuable asset in the management of this condition.
Additionally, Barnidipine is used as a diuretic agent for patients with renal parenchymal hypertension. Its dual action as an antihypertensive and diuretic makes it a potential candidate in the treatment of patients with this specific type of hypertension.

Originator

Yamanouchi (Japan)

Therapeutic Function

Coronary vasodilator

in vitro

the effects of barnidipine on l-type ca(2+) current (i(ca(l))) were investigated in rat ventricular cardiomyocytes. it was found that barnidipine reduced i(ca(l)) in a concentration and voltage dependent manne. barnidipine induced a leftward shift of the steady-state inactivation curve of i(ca(l)) [1].

in vivo

a previous study was conducted to investigate the influence of barnidipine treatment on early stage hypertension by determining the mesenteric and renal arteries as well as the kidney in l-name-induced hypertensive rats. barnidipine was applied to rats after 2 weeks of l-name administration, and continued for the next 3 weeks concomitantly with l-name. histopathological studies verified structural alterations in the arteries and the kidney. moreover, a decrease in endothelial nitric oxide synthase expression was observed both in the arteries and kidney of hypertensive rats with barnidipine treatment [2].

references

[1] wegener jw, meyrer h, rupp j, nawrath h. barnidipine block of l-type ca(2+) channel currents in rat ventricular cardiomyocytes. br j pharmacol. 2000 aug;130(8):2015-23.[2] alp yildirim fi, eker kizilay d, ergin b, balci ekmeki, topal g, kucur m, demirci tansel c, uyde doan bs. barnidipine ameliorates the vascular and renal injury in l-name-induced hypertensive rats. eur j pharmacol. 2015 oct 5;764:433-42. [3] derosa g, mugellini a, pesce rm, d'angelo a, maffioli p. barnidipine compared to lercanidipine in addition to losartan on endothelial damage and oxidative stress parameters in patients with hypertension and type 2 diabetes mellitus. bmc cardiovasc disord. 2016 apr 12;16:66.

InChI:InChI=1/C27H29N3O6.ClH/c1-17-23(26(31)35-3)25(20-10-7-11-21(14-20)30(33)34)24(18(2)28-17)27(32)36-22-12-13-29(16-22)15-19-8-5-4-6-9-19;/h4-11,14,22,25,28H,12-13,15-16H2,1-3H3;1H/t22-,25-;/m0./s1

Upstream product

• 76093-34-0 (+)-(S)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine-3-carboxylic acid 
• 101385-90-4 (S)-N-benzyl-3-hydroxypyrrolidine 
• 88712-56-5 1,4-dihydro-2,6-dimethyl-3-methoxycarbonyl-4-(3-nitrophenyl)-pyridine-5-carboxylic acid chloride 
• 104713-75-9 barnidipine 
• 74936-72-4 5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid 
• 75130-24-4 2,6-dimethyl-4-(3-nitrophenyl)-5-methoxycarbonyl-1,4-dihydropyridine-3-carboxylic acid 2-cyanoethyl ester 
• 102993-38-4 2-cyanoethyl 2-(3-nitrobenzylidene)-3-oxobutanoate 
• 99-61-6 3-nitro-benzaldehyde 
• 100-46-9 benzylamine 
• 101469-91-4 (3S)-1-benzyl-3-hydroxypyrrolidine-2,5-dione 
• 775-15-5 1-benzyl-3-pyrrolidinol 
• 76093-33-9 (R)-5-(methoxycarbonyl)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid 
• 88712-56-5 methyl (R)-5-chlorocarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate 

Downstream Products

• 76093-33-9 (R)-5-(methoxycarbonyl)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid 
• 172331-68-9 2,6-Dimethyl-4-(3-nitro-phenyl)-pyridine-3,5-dicarboxylic acid 3-((S)-1-benzyl-pyrrolidin-3-yl) ester 5-methyl ester 

Related news

General paperHemodynamic effects of Barnidipine (cas 104757-53-1) hydrochloride in conscious squirrel monkeys09/07/2019

1.1. The effects of barnidipine, a new dihydropyridine Ca2+ antagonist, on cardiovascular and renin-angiotensin-aldosterone systems were investigated in conscious squirrel monkeys.2.2. Barnidipine (0.3–3 mg/kg p.o.) produced a dose-related decrease in systolic blood pressure. The hypotensive ac...detailed

Antihypertensive effect of Barnidipine (cas 104757-53-1) 10 mg or amlodipine 5 to 10 mg once daily in treatment-naive patients with essential hypertension: A 24-week, randomized, open-label, pilot study09/06/2019

Background: Dihydropyridine calcium antagonists are largely employed for the treatment of hypertension, coronary heart disease, and heart failure.Objective: The aim of our study was to compare the antihypertensive effect of the dihydropyridine calcium antagonists barnidipine and amlodipine.Metho...detailed

Effects of Barnidipine (cas 104757-53-1) hydrochloride, a calcium channel blocker, on renal microcirculation in rats: a pilot study09/05/2019

Barnidipine hydrochloride, a dihydropyridine calcium channel blocker, increases both renal blood flow and glomerular filtration while effectively reducing blood pressure. The goal of the present study was to determine the effects of barnidipine on renal microcirculation. We used the rat in vivo ...detailed

Sensitive and specific liquid chromatographic–tandem mass spectrometric assay for Barnidipine (cas 104757-53-1) in human plasma09/04/2019

A sensitive and specific LC–MS–MS assay has been developed and validated for barnidipine (1-benzyl-3-pyrrolidinyl)methyl-2,6-dimethyl-4(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate). The assay involves a simple and rapid solid-phase extraction procedure. Sample analysis was on a Spheri...detailed

Antihypertensive efficacy and tolerability of Barnidipine (cas 104757-53-1) hydrochloride in patients with renal parenchymal hypertension09/03/2019

ObjectiveThe goal of this study was to assess the therapeutic efficacy and tolerability of barnidipine hydrochloride in patients with renal parenchymal hypertension.detailed

Different photodegradation behavior of Barnidipine (cas 104757-53-1) under natural and forced irradiation09/02/2019

An in depth study on photodegradation of barnidipine, a new 1,4-dihydropyridine antihypertensive drug, was performed by exposing the drug to natural and stressing light irradiation. A different degradation process and distribution of photoproducts under different light sources and irradiation po...detailed

Cardiovascular pharmacologyPerindopril and Barnidipine (cas 104757-53-1) alone or combined with simvastatin on hepatic steatosis and inflammatory parameters in hypertensive patients08/31/2019

The aim of this study was to evaluate the effects of perindopril or barnidipine alone or combined with simvastatin on metabolic parameters and hepatic steatosis degree.One hundred and forty nine mild to moderate hypertensive, normocholesterolemic, overweight or obese outpatients with hepatic ste...detailed

Relevant articles and documents

Barnidipine hydrochloride compound and preparation method thereof

The invention discloses a barnidipine hydrochloride compound and a preparation method thereof. The preparation method comprises the following steps: (1) using 3-hydroxypropionitrile to react with diketene, to obtain an intermediate 1; (2) enabling the intermediate 1 to react with m-nitrobenzaldehyde and Beta-amino methyl crotonate, to obtain an intermediate 2; (3) enabling the intermediate 2 to behydrolyzed by strong base, to obtain an intermediate 3; (4) enabling the intermediate 3 to be resolved by chiral organic base, to obtain an intermediate 4; (5) enabling the intermediate 4 to react with thionyl chloride, (S)-1-benzyl-3-pyrrolidinol, and HCI ethanol solution, to obtain a crude product of barnidipine hydrochloride; and (6) performing ethyl alcohol pulping and refining, and ethyl alcohol recrystallization on the crude product of the barnidipine hydrochloride, to obtain the barnidipine hydrochloride.

Synthesis and characterization of impurities of barnidipine hydrochloride, an antihypertensive drug substance

Barnidipine hydrochloride is a long term dihydropyridine calcium channel blocker used for the treatment of hypertension. During the process development of barnidipine hydrochloride, four barnidipine impurities were detected by high-performance liquid chromatography (HPLC) with an ordinary column (Agilent ZORBAX Eclipse XDB-C18, 150 mm × 4.6 mm, 5 m). All these impurities were identified, synthesized, and subsequently characterized by their respective spectral data (MS, 1H-NMR, and 13C-NMR). The identification of these impurities should be useful for quality control in the manufacture of barnidipine.

Stereoselectivity of a Potent Calcium Antagonist, 1-Benzyl-3-pyrrolidinyl Methyl 2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated.The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a*HBr as well as 3a*HCl.The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation.The potency order of the four enantiomers was (S,S)-3a > (S,R)-3b > (R,R)-3d > (R,S)-3c.Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a*HCl or 3a*HBr.On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5.The conformational restriction may be a factor causing stereoselectivity of antagonism.