21829-25-4 Usage
Pharmacological effects
Nifedipine is a kind of dihydropyridine calcium antagonists, it can inhibit the Ca2 + uptake of cardiac and vascular smooth muscles, and it can expand the coronary artery , increase coronary blood flow,and improve myocardial ischemic tolerance, at the same time, it can expand peripheral arteries and reduce peripheral vascular resistance,and relieve coronary artery spasm, and increase coronary blood flow, improve myocardial ischemia,in order to decrease the blood pressure. Small doses do not affect blood pressure, when expanding coronary artery ,it is a better anti-angina drug .It is used for the prevention and treatment of angina pectoris,with no adverse effects on respiratory function, its efficacy is best particularly for angina pectoris coronary spasm and obstructive airway disease with angina , its efficacy is superior to β-blockers.It is also applied to all types of high blood pressure, including severe and resistant hypertension. Treatment of refractory congestive heart failure may be taking this long. It is also used for the treatment of primary pulmonary hypertension, diffuse esophageal spasm and bronchial asthma, duodenal ulcers, urinary tract obstruction, exercise-induced asthma, achalasia.
Nifedipine has a certain selectivity on vascular smooth muscles , the direct negative inotropic effect and denaturation effect on the heart are weak, systemic administration of it does not cause the heart rate slowing down ,on the contrary, the heart rate performances reflected increase.
The above information is edited by the lookchem of Tian Ye.
Chemical properties
Yellow crystals. Melting point 172-174 ℃. Soluble in acetone, chloroform, ethyl acetate, dissolved in hot methanol, insoluble in water. It easily deteriorates in case of light.
Uses
Different sources of media describe the Uses of 21829-25-4 differently. You can refer to the following data:
1. Long-term coronary vasodilators. This product can increase coronary blood flow, reducing myocardial oxygen consumption.it is used for acute and chronic coronary insufficiency,especially the angina and myocardial infarction.
2. Used as an antihypertensive and antianginal. A dihydorpyridine calcium channel blocker
3. Nifedipine is used for preventing and relieving angina pectoris attacks, for hypertension,
and as an ingredient in combination therapy for chronic cardiac insufficiency.
4. For the management of vasospastic angina, chronic stable angina, hypertension, and Raynaud's phenomenon. May be used as a first line agent for left ventricular hypertrophy and isolated systolic hypertension (long-acting agents).
Production methods
O-nitrobenzaldehyde, methyl acetoacetate, methanol, ammonia are refluxed together , then froze , crystallize,after filtration, nifedipine crude is obtained . The crude product is recrystallized through methanol .then the product is derived , yield rate is 50%.
Category
Toxic substances
Toxicity grading
Highly toxic
Acute toxicity
Oral-rat LD50: 1022 mg/kg; Oral-Mouse LD50: 310 mg/kg.
Flammability and hazard characteristics
Combustion produces toxic fumes of nitrogen oxides; medicinal side effects: low blood pressure, cardiac disease, local blood flow disease, high blood sugar, psychosis.
Storage Characteristics
Ventilated , low-temperature, drying; and it is kept separately from food raw materials warehouse.
Extinguishing agent
Dry powder, foam, sand, carbon dioxide, water spray.
Description
Nifedipine (21829-25-4) is a clinically useful L-type calcium blocker.
Chemical Properties
Yellow Crystalline Solid
Originator
Adalat,Bayer,W. Germany,1975
Manufacturing Process
45 grams 2-nitrobenzaldehyde, 80 cc acetoacetic acid methyl ester, 75 cc
methanol and 32 cc ammonia are heated under reflux for several hours,
filtered off, cooled and, after suction-filtration, 75 grams of yellow crystals of
MP 172° to 174°C are obtained, according to US Patent 3,485,847.
Brand name
Adalat (Bayer); Afeditab (Watson);Procardia (Pfizer).
Therapeutic Function
Coronary vasodilator
World Health Organization (WHO)
Nifedipine is a dihydropyridine calcium channel blocker. It is
listed in the WHO Model List of Essential Drugs. The 10mg tablet is retained on the
list for short-term treatment of hypertension. Sustained-release preparations are
advised for long-term treatment.
General Description
Different sources of media describe the General Description of 21829-25-4 differently. You can refer to the following data:
1. Nifedipine, 1,4-dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate dimethyl ester(Adalat, Procardia), is a dihydropyridine derivative thatbears no structural resemblance to the other calcium antagonists.It is not a nitrate, but its nitro group is essential for itsantianginal effect. As a class, the dihydropyridines possessa central pyridine ring that is partially saturated. To this, positions2 and 6 are substituted with an alkyl group that mayplay a role in the agent’s duration of action. In addition, positions3 and 5 are carboxylic groups that must be protectedwith an ester functional group. Depending on the type ofester used at these sites, the agent can be distributed to variousparts of the body. Finally, position 4 requires an aromaticsubstitution possessing an electron-withdrawinggroup (i.e., Cl or NO2) in the ortho and/or meta position.
2. Odorless yellow crystals or powder. Tasteless.
Air & Water Reactions
Aqueous solutions are very sensitive to light. . Insoluble in water.
Reactivity Profile
Nifedipine is sensitive to light.
Fire Hazard
Flash point data for Nifedipine are not available; however, Nifedipine is probably combustible.
Biological Activity
L-type calcium channel blocker.
Biochem/physiol Actions
Nifedipine is a L-type Ca2+ channel blocker; and induces apoptosis in human glioblastoma cells. Nifedipine has neuroprotection activity and protects substantia nigra. Nifedipine has antioxidant potential. Nifedipine downregulates inflammatory cytokines like macrophage inflammatory protein-2 (MIP-2), tumor necrosis factor-α (TNF-α). Nifedipine has antihypertensive properties. Nifedipine inhibits extracellular region of adenosine A2a receptor (ADORA2A) gene.
Mechanism of action
Nifedipin causes relaxation of smooth musculature, dilation of coronary and peripheral
arteries, and reduction of peripheral resistance and arterial blood pressure, and enhances
oxygen supply to the heart.
Clinical Use
The prototype of this class, nifedipine, has potent peripheralvasodilatory properties. It inhibits the voltage-dependentcalcium channel in the vascular smooth muscle but has littleor no direct depressant effect on the SA or AV nodes, eventhough it inhibits calcium current in normal and isolated cardiactissues. Nifedipine is more effective in patients whoseanginal episodes are caused by coronary vasospasm and isused in the treatment of vasospastic angina as well as classicangina pectoris. Because of its strong vasodilatory properties,it is used in selected patients to treat hypertension.
Synthesis
Nifedipine, dimethyl ether 1,4-dihydro-2,6-dimethyl-4-(2′-nitrophenyl)-3,5-
piridindicarboxylic acid (19.3.16), is synthesized by a Hantsch synthesis from two
molecules of a β-dicarbonyl compound—methyl acetoacetate, using as the aldehyde component—
2-nitrobenzaldehyde and ammonia. The sequence of the intermediate stages of
synthesis has not been completely established.
Drug interactions
Potentially hazardous interactions with other drugs
Aminophylline: possibly increases aminophylline
concentration.
Anaesthetics: enhanced hypotensive effect.
Anti-arrhythmics: concentration of dronedarone
increased.
Antibacterials: metabolism accelerated by rifampicin;
metabolism possibly inhibited by clarithromycin,
erythromycin and telithromycin.
Antidepressants: metabolism possibly inhibited by
fluoxetine; concentration reduced by St John’s wort;
enhanced hypotensive effect with MAOIs.
Antiepileptics: effect reduced by carbamazepine,
barbiturates, phenytoin and primidone.
Antifungals: metabolism possibly inhibited by
itraconazole and ketoconazole; concentration
increased by micafungin; negative inotropic effect
possibly increased with itraconazole.
Antihypertensives: enhanced hypotensive effect,
increased risk of first dose hypotensive effect of
post-synaptic alpha-blockers; occasionally severe
hypotension and heart failure with beta-blockers.
Antivirals: concentration possibly increased by
ritonavir; use telaprevir with caution.
Cardiac glycosides: digoxin concentration possibly
increased.
Ciclosporin: may increase ciclosporin level, but not a
problem in practice; nifedipine concentration may be
increased.
Cytotoxics: metabolism of vincristine possibly
reduced.
Grapefruit juice: concentration increased - avoid.
Magnesium salts: profound hypotension with IV
magnesium.
Tacrolimus: increased tacro
Metabolism
Nifedipine is metabolised in the gut wall and oxidised in
the liver via the cytochrome P450 isoenzyme CYP3A4, to
inactive metabolites.
Excreted mainly as metabolites via the kidney
References
1) Vater et al., (1972), (Pharmacology of 4-(2′-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (Nifedipine, BAY a 1040); Arzneimittelforschung, 22 1
Check Digit Verification of cas no
The CAS Registry Mumber 21829-25-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,1,8,2 and 9 respectively; the second part has 2 digits, 2 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 21829-25:
(7*2)+(6*1)+(5*8)+(4*2)+(3*9)+(2*2)+(1*5)=104
104 % 10 = 4
So 21829-25-4 is a valid CAS Registry Number.
InChI:InChI=1/C17H18N2O6/c1-9-13(16(20)24-3)15(14(10(2)18-9)17(21)25-4)11-7-5-6-8-12(11)19(22)23/h5-8,13,15H,1-4H3/t13?,15-/m1/s1
21829-25-4Relevant articles and documents
Protective role of the novel hybrid 3,5-dipalmitoyl-nifedipine in a cardiomyoblast culture subjected to simulated ischemia/reperfusion
Santa-Helena, Eduarda,Teixeira, Stefanie,Castro, Micheli Rosa de,Cabrera, Diego da Costa,D'Oca, Caroline Da Ros Montes,D'Oca, Marcelo G. Montes,Votto, Ana Paula S.,Nery, Luiz Eduardo Maia,Gon?alves, Carla Amorim Neves
, p. 356 - 364 (2017)
This work investigated the acute effects of the calcium channel blocker nifedipine and its new fatty hybrid derived from palmitic acid, 3,5-dipalmitoyl-nifedipine, compared to endocannabinoid anandamide during the process of inducing ischemia and reperfusion in cardiomyoblast H9c2 heart cells. The cardiomyoblasts were treated in 24 or 96-well plates (according to the test being performed) and maintaining the treatment until the end of hypoxia induction. The molecules were tested at concentrations of 10 and 100?μM, cells were treated 24?h after assembling the experimental plates and immediately before the I/R. Cell viability, apoptosis and necrosis, and generation of reactive oxygen species were evaluated. Nifedipine and 3,5-dipalmitoyl-nifedipine were used to assess radical scavenging potential and metal chelation. All tested molecules managed to reduce the levels of reactive oxygen species compared to the starvation?+?vehicle group. In in vitro assays, 3,5-dipalmitoyl-nifedipine showed more antioxidant activity than nifedipine. These results indicate the ability of this molecule to act as a powerful ROS scavenger. Cell viability was highest when cells were induced to I/R by both concentrations of anandamide and the higher concentration of DPN. These treatments also reduced cell death. Therefore, it was demonstrated that the process of hybridization of nifedipine with two palmitic acid chains assigns a greater cardioprotective effect to this molecule, thereby reducing the damage caused by hypoxia and reoxygenation in cardiomyoblast cultures.
Approaches to combinatorial synthesis of heterocycles: A solid-phase synthesis of 1,4-dihydropyridines
Gordeev, Mikhail F.,Patel, Dinesh V.,Gordon, Eric M.
, p. 924 - 928 (1996)
N-Immobilized enamino esters 2 derived from amine-functionalized PAL or Rink polystyrene resins react with preformed 2-arylidene β-keto esters or directly with β-keto esters and aldehydes to afford, upon trifluoroacetic acid cleavage, 1,4-dihydropyridine (DHP) derivatives in good yields. The mechanism of this transformation on solid support has been studied using 13C NMR and IR spectroscopies. This new solid-phase synthesis has been applied to the preparation of several bioactive DHPs and is designed to be amenable to the 'split and pool' protocol for combinatorial library synthesis.
Aqueous CO2fixation: construction of pyridine skeletons in cooperation with ammonium cations
Fan, Weibin,Guo, Shiwei,Huang, Deguang,Li, Yinghua,Xiang, Shiqun,Zhang, Wei
supporting information, p. 7950 - 7955 (2021/10/29)
A simple and green method is explored for the synthesis of fused pyridines by [2 + 2 + 1 + 1] the cycloaddition of ketones with an ammonium cation under a CO2atmosphere. The reactions employed ammonium cation as a nitrogen source and CO2gas as a carbon source in an aqueous solution. Monoethanolamine (MEA) was used as an additive to increase the solubility of CO2in an aqueous solution. The scope and versatility of the method are demonstrated with 38 examples. Products are found to be photosensitive and show potential applications as organic optoelectronic materials. A selectfluor-promoted reaction mechanism is proposed based on the experimental studies. Our work is superior as it is a metal-free system, uses CO2as a carbon source and MEA as an additive in aqueous synthesis.
METHODS FOR TREATING CHRONIC FATIGUE SYNDROME AND MYALGIC ENCEPHALOMYELITIS
-
, (2021/03/13)
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.
Preparation method and application of novel ionic beta-naphthol aldehyde Schiff base zirconium complex
-
Paragraph 0041; 0070-0071, (2019/12/02)
The invention belongs to the technical field of catalytic organic synthesis, and particularly relates to a preparation method and application of a novel ionic beta-naphthol aldehyde Schiff base zirconium complex. Zirconium atoms are coordinated with a beta-naphthol aldehyde Schiff base ligand and water molecules, and two perfluoroalkyl (aryl) sulfonic acid groups are combined with central atom zirconium through covalent bonds and ionic bonds respectively. The preparation method comprises the following steps: dissolving beta-naphthol aldehyde Schiff base zirconium dichloride in a solvent, adding a silver salt under the protection of N2, reacting the mixture for 1-4 hours in a dark place at room temperature, performing filtration, adding n-hexane into filtrate until layering, putting the solution into a refrigerator, and freezing the solution for 24 hours to separate out the beta-naphthol aldehyde Schiff base zirconium complex. The beta-naphthol aldehyde Schiff base zirconium complex hashigh air stability and strong Lewis acidity, and can efficiently catalyze the Hantzsch reaction of aldehyde, beta-ketoester and ammonium acetate to synthesize 1,4-dihydropyridine derivatives.
