54527-84-3

Basic information

• Product Name: Nicardipine hydrochloride
• Synonyms: 2-(benzylmethylamino)ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylatemonohydrochloride;Naratriptan HCl;NICARDIPINE HYDROCHLORIDE (YC-93) CALCIU M CHANNEL ANTAG;NICARDIPINE HYDROCHLORIDE MM(CRM STANDARD);1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic Acid Methyl 2-[Methyl(phenylmethyl)amino]ethyl Ester Hydrochloride;Antagonyl;Barizin;Dacarel
• CAS NO: 54527-84-3
• Molecular Formula: C₂₆H₂₉N₃O₆*ClH
• Molecular Weight: 515.99
• EINECS: 259-198-4
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Calcium channel;TRONOLANE;Cardiovascular APIs
• Mol File: 54527-84-3.mol

Chemical Properties

• Melting Point: 176-1780C
• Boiling Point: 603.4 °C at 760 mmHg
• Flash Point: 318.7 °C
• Appearance: yellow/powder
• Vapor Pressure: 1.63E-14mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: DMSO: ~1 mg/mL
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in distilled water or ethanol may be stored at -20°C for up to 1 month.
• Merck: 14,6495
• CAS DataBase Reference: Nicardipine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Nicardipine hydrochloride(54527-84-3)
• EPA Substance Registry System: Nicardipine hydrochloride(54527-84-3)

Safety Data

• Hazard Codes: T
• Statements: 23/24/25
• Safety Statements: 36/37/39-45
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: US7972100
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 54527-84-3(Hazardous Substances Data)

Usage

Uses

1. Used in Pharmaceutical Industry:
Nicardipine hydrochloride is used as an antihypertensive agent for the treatment of mild, moderate, and severe hypertension. It helps in managing high blood pressure by dilating blood vessels, which allows for better blood flow and reduces the workload on the heart.
2. Used in Cardiology:
Nicardipine hydrochloride is used as an antianginal agent for the management of stable angina. It helps to alleviate chest pain and discomfort caused by insufficient blood supply to the heart muscles by improving blood flow to the heart.
3. Used in Anesthetic Applications:
Nicardipine hydrochloride is used as a topical anesthetic, providing localized pain relief and numbing effects on the skin or mucous membranes.
4. Used in Research and Development:
Nicardipine hydrochloride is utilized in research for its ability to inhibit adenosine receptors and cytochrome P450 3A4, as well as its activation of transient receptor potential A1 channels, which can be valuable in studying various physiological and pathological processes.

Biochem/physiol Actions

Blocks L-type voltage-dependent calcium channels; antihypertensive.

Clinical Use

Calcium-channel blocker: Prophylaxis and treatment of angina Mild to moderate hypertension Acute life-threatening hypertension and post operative hypertension (IV)

Safety Profile

Poison by ingestion, intravenous, and intraperitoneal routes. Moderately toxic by subcutaneous route. Human systemic effects: decreased urine volume or anuria. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of NOx an

Drug interactions

Potentially hazardous interactions with other drugs Aminophylline: possibly increases aminophylline concentration. Anaesthetics: enhanced hypotensive effect. Antibacterials: metabolism possibly accelerated by rifampicin; metabolism possibly inhibited by clarithromycin, erythromycin and telithromycin. Antidepressants: enhanced hypotensive effect with MAOIs. Antiepileptics: effect reduced by carbamazepine, barbiturates, phenytoin and primidone. Antifungals: metabolism possibly inhibited by itraconazole and ketoconazole; negative inotropic effect possibly increased with itraconazole. Antihypertensives: enhanced hypotensive effect, increased risk of first dose hypotensive effect of post synaptic alpha-blockers. Antivirals: concentration possibly increased by ritonavir; use telaprevir with caution. Cardiac glycosides: digoxin concentration increased. Ciclosporin: concentration of ciclosporin increased Grapefruit juice: concentration increased - avoid. Tacrolimus: may increase tacrolimus levels. Theophylline: possibly increased theophylline concentration.

Metabolism

Nicardipine is subject to saturable first-pass metabolism. It is extensively metabolised in the liver and excreted in the urine and faeces, mainly as inactive metabolites.

References

1) Merck 14 6495 2) Hulubei et al. (2012), 4-Isoxazolyl-1,4-dihydropyridines exhibit binding at the multidrug-resistance transporter; Bioorg. Med. Chem., 20 6620

InChI:InChI=1/C26H29N3O6.ClH/c1-17-22(25(30)34-4)24(20-11-8-12-21(15-20)29(32)33)23(18(2)27-17)26(31)35-14-13-28(3)16-19-9-6-5-7-10-19;/h5-12,15,24,27H,13-14,16H2,1-4H3;1H

Upstream product

• 101-98-4 2-(N-benzyl-N-methyl)amino-1-ethanol 
• 99-61-6 3-nitro-benzaldehyde 
• 14205-39-1 methyl 3-aminocrotonate 
• 54527-65-0 acetoacetic acid [2-(N-methyl-N-benzylamino)-ethyl]-ester 
• 14205-39-1 methyl (E)-3-aminocrotonate 
• 39562-17-9 methyl 2-(3-nitrophenylmethylene)acetoacetate 
• 54527-73-0 2-(N-benzyl-N-methylamino)-ethyl 3-aminocrotonate 
• 85677-95-8 2-hydroxyethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate 
• 103785-47-3 methanesulfonyloxyethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate 
• 103-67-3 benzyl-methyl-amine 

Downstream Products

• 101-98-4 2-(N-benzyl-N-methyl)amino-1-ethanol 
• 1259327-68-8 C₁₆H₁₅N₂O₆^(1-)*Na⁽¹⁺⁾ 
• 69441-29-8 2,6-Dimethyl-4-(3-nitro-phenyl)-pyridine-3,5-dicarboxylic acid 3-[2-(benzyl-methyl-amino)-ethyl] ester 5-methyl ester; hydrochloride 

Relevant articles and documents

METHODS FOR TREATING CHRONIC FATIGUE SYNDROME AND MYALGIC ENCEPHALOMYELITIS

In one aspect the invention relates to a method of treatment selected from the group consisting of: (a) treating a symptom such as pain in a subject identified or diagnosed as having Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); (b) treating a symptom such as pain in a subject having dysfunctional TRPM3 ion channel activity; (c) restoring NK cell function in a subject having dysfunctional TRPM3 ion channel activity; and (d) restoring calcium homeostasis in a subject having dysfunctional TRPM3 ion channel activity. The method comprises the step of administering to the subject a therapeutically effective amount of at least one therapeutic compound selected from the group consisting of: (i) an opioid receptor antagonist; (ii) an opioid antagonist; and (iii) a therapeutic compound that restores TRPM3 ion channel activity. In some embodiments the therapeutic compound is naltrexone hydrochloride.

Advanced Continuous Flow Platform for On-Demand Pharmaceutical Manufacturing

As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy time-scale, we previously reported a refrigerator-sized continuous flow system for the on-demand production of essential medicines. Building on this technology, herein we report a second-generation, reconfigurable and 25 % smaller (by volume) continuous flow pharmaceutical manufacturing platform featuring advances in reaction and purification equipment. Consisting of two compact [0.7 (L)×0.5 (D)×1.3 m (H)] stand-alone units for synthesis and purification/formulation processes, the capabilities of this automated system are demonstrated with the synthesis of nicardipine hydrochloride and the production of concentrated liquid doses of ciprofloxacin hydrochloride, neostigmine methylsulfate and rufinamide that meet US Pharmacopeia standards.

Processes of manufacturing substituted-1,4-dihydropyridines, improved aqueous solutions thereof, and processes of manufacturing the solutions

A process of preparing a stable parenteral solution of a 1,4-dihydropyridine salt, such as nicardipine hydrochloride, in an acidic aqueous medium. The presence of L-arginine in the solution enhances the solubility of the salt, which is poorly soluble in water. An aqueous, injectable isotonic solution at pH about 3.5-3.6 consists essentially of nicardipine hydrochloride, L-arginine, and a sugar alcohol. An improved single pot manufacturing process for obtaining unsymmetrical 1,4-dihydropyridines by using more than one mole equivalent of aldehyde with respect to the other reactants (amino crotonate and acetoacetate ester). The reaction can be conducted in a solvent present at 20 times the amount of any one component. A process for changing one polymorph of nicardipine hydrochloride (Form A) into another (Form B), and a separate process for the reverse (Form B into Form A).

Novel process for producing 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate-3-methyl ester-5-beta-(N-benzyl-N-methylamino)ethyl ester

Nicardipine hydrochloride, i.e. 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 3-methyl ester-5-β-(N-benzyl-N-methylamino)ethyl ester, is prepared in a short time at a high yield by reacting, in a non-aqueous system, m-nitrobenzaldehyde or another compound of formula (1) wherein either R1 and R2 are taken together and represent =O or =N-lower alkyl, or R1 represents -O-, R2 represents -NH-, and R1 and R2 are linked via C2 4 straight or branched-chain alkylene to form a saturated heterocyclic ring which may be substituted, simultaneously or sequentially, in either order, with methyl 3-aminocrotonate and (N-methyl-N-benzylamino)ethyl 3-aminocrotonate.

Inclusion complex of nicardipine or its hydrochloride with beta-cyclodextrin, a process for preparing the same and a sustained release pharmaceutical preparation containing the same

There is described a new inclusion complex of nicardipine or its hydrochloride with beta-cyclodextrin, which is prepared by admixing nicardipine or its hydrochloride with beta--cyclodextrin in a molar ratio of the compounds 1:0.9-1.1 under stirring at a temperature from about room temperature to the boiling temprature of the reaction mixture in an aqueous or ethanolic medium, cooling the reaction mixture to 0 ° to 5 °C and isolating the desired complex. The inclusion complex of nicardipine or its hydrochloride pos-sesses cerebrovascular-vasodilatory and coronary-vasodilatory properties, which are equally well expressed as those of nicar-dipine or its hydrochloride themselves, yet owing to the better solubility of the complex at a higher pH range, such as it ex-ists e.g. in the intestinal tract, the manufacture of sustained release pharmaceutical forms is made possible, whereby a greater extent of dissolution of the active substance is provided also in the intestinal juice.

Pyridyl ester containing 1,4-dihydropyridine derivatives and salts thereof and pharmaceutical composition containing the same

This invention relates to a novel 1,4-dihydropyridine derivative of the formula STR1 wherein R2 is pyridyl, or a salt thereof. These compounds have a vasodilating activity and a platelet aggregation inhibiting activity. Also disclosed are pharmaceutical compositions containing the same.

Vasodilating and platelet aggregation inhibiting 1,4 dihydropyridines with an imidazolyl or pyridyl containing ester

This invention relates to a 1,4-dihydropyridine derivative of the formula STR1 wherein Y represents an oxygen or sulfur atom or a vinylene group, Z represents an oxygen or sulfur atom or an alkylene group, R2 represents an imidazolyl or pyridyl group and the remaining substituents are herein defined. These compounds have a vasodilating activity and a platelet aggregation inhibiting activity.

1,4-Dihydropyridine derivatives

There are provided novel 1,4-dihydropyridine derivatives, particularly 2,6-dimethyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-β-(N-benzyl-N-methylamino)ethyl ester and 5-methyl ester. The 1,4-dihydropyridine derivatives are characterized by cerebral vascular dilator activity.