3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

• ChemBase ID: 986
• Molecular Formular: C17H18N2O6
• Molecular Mass: 346.33462
• Monoisotopic Mass: 346.11648631
• SMILES: O(C(=O)C1=C(NC(=C(C1c1c([N+](=O)[O-])cccc1)C(=O)OC)C)C)C
• Canonical SMILES: COC(=O)C1=C(C)NC(=C(C1c1ccccc1[N+](=O)[O-])C(=O)OC)C
• InChI: InChI=1S/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/h5-8,15,18H,1-4H3
• InChIKey: HYIMSNHJOBLJNT-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• IUPAC Traditional name: procardia xl; 3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• Brand Name: Adalat; Adalat 10; Adalat 20; Adalat 5; Adalat CC; Adalat CR; Adalat Crono; Adalat Ft; Adalat Gits; Adalat Gits 30; Adalat LA; Adalat LP; Adalat Oros; Adalat PA; Adalat Retard; Adalate; Adapine; Adapress; Alat; Aldipin; Alfadal; Alonix; Alonix S; Alpha-Nifedipine Retard; Angipec; Anifed; Anpine; Apo-Nifed; Aprical; Bonacid; Calcibloc; Calcigard; Calcilat; Camont; Cardifen; Cardilat; Cardionorm; Chronadalate; Chronadalate Lp; Citilat; Coracten; Coral; Cordafen; Cordaflex; Cordalat; Cordicant; Cordilan; Cordipin; Corinfar; Corotrend; Corynphar; Depin; Dignokonstant; Dilafed; Dilcor; Dipinkor; Duranifin; Ecodipi; Ecodipin; Ecodipin E; Fedcor; Fedcor Retard; Fenamon; Fenamon Sr; Fenihidin; Fenihidine; Glopir; Hadipin; Hexadilat; Introcar; Kordafen; Macorel; Megalat; Myogard; N1fedilat; Nedipin; Nicardia; Nifangin; Nifar; Nifdemin; Nifebene; Nifecard; Nifecor; Nifedepat; Nifedicor; Nifedin; Nifedine; Nifedipine Retard; Nifedipres; Nifedirex LP; Nifelan; Nifelat; Nifelat Q; Nifelate; Nifensar XL; Nificard; Nifidine; Nifipen; Niphedipine; Orix; Oxcord; Pidilat; Procardia; Procardia XL; Sepamit; Tibricol; Zenusin; Adalat, Procardia
• Synonyms: Nifedipine; Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate; Anifed; Afeditab CR; Nifediac; Nifedical; 3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate; Adalate; Aldipine; Cardiate; 1,4-Dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine-dicarboxylic acid dimethyl ester; 1,4-Dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester; Nifedipine; Adalat; Adipine; Angiopine; Calanif; Calcilat; Cardilate; Coracten; Coroday; Fenihidine; Fortipine; Glopir; Hypolar Retard; Nifecor; Nifedicor; Nifedipress; Nifelat; Nifedotard; Nifensar XL; Nimodrel; Nivaten; Procardia; Slofedipine; Tensipine

Database IDs

• CAS Number: 21829-25-4
• EC Number: 244-598-3
• MDL Number: MFCD00057326
• PubChem SID: 24277855; 160964449; 46505103
• PubChem CID: 4485
• CHEBI ID: 7565
• ATC CODE: C08CA05
• CHEMBL: 193
• Chemspider ID: 4330
• DrugBank ID: DB01115
• IUPHAR ligand ID: 2514
• KEGG ID: D00437
• Unique Ingredient Identifier: I9ZF7L6G2L
• Wikipedia Title: Nifedipine
• Medline Plus: a684028

CALCULATED PROPERTIES

JChem

• H Acceptors: 5
• H Donor: 1
• LogD (pH = 5.5): 1.5918752
• LogD (pH = 7.4): 1.8118262
• Log P: 1.8154943
• Molar Refractivity: 92.1647 cm^3
• Polarizability: 33.98248 Å^3
• Polar Surface Area: 110.45 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.49
• LOG S: -4.29
• Solubility (Water): 1.77e-02 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO: soluble; ethanol: soluble; Insoluble; Methanol
• Apperance: yellow powder; Yellow Solid
• Melting Point: 171 - 175°C; 172-174°C; 172-174°C; 173°C (343.4°F)
• Hydrophobicity(logP): 2; 3.406

Safety Information

• Storage Condition: -20°C; -20°C Freezer; Room Temperature (15-30°C)
• Storage Warning: IRRITANT
• RTECS: US7975000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 1
• Risk Statements: 22; R:22
• Safety Statements: 26-36; S:36/37/39
• TSCA Listed: false
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves
• Storage Temperature: 2-8°C

Pharmacology Properties

• Admin Routes: Oral
• Bioavailability: 45-56%
• Excretion: Renal: >50%, Biliary: 5-15%
• Half Life: 2 hours
• Metabolism: Gastrointestinal, Hepatic
• Protein Bound: 92-98%
• Pregnancy Category: C: (USA)
• Gene Information: human ... ADORA2A(135), ADORA3(140), CACNA2D1(781), CYP1A2(1544), KCNH1(3756), TTR(7276)mouse ... Cacna1c(12288)rat ... Adora1(29290), Adora2a(25369), Cacna1c(24239), Cacna1d(29716), Kcnj1(24521), Kcnn4(65206), Tbxas1(24886)
• Mechanism of Action: Calcium channel blocker; causing dilation of the coronary and systemic arteries,; increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.; Inhibits the influx of extracellular calcium through myocardial and vascular membrane pores by physically plugging the channel; The decrease in intracellular calcium inhibits the contractile processes of smooth muscle cells,

Product Information

• Purity: ≥98% (HPLC); 95%
• Salt Data: Free Base
• Application(s): Antihypertensive agent; Coronary vasodilator; Used to treat Prinzmetal's angina, hypertension, and other vascular disorders such as Raynaud's phenomenon

DETAILS

MP Biomedicals - 02151743

Purity: 95%
Yellow crystalline powder
A calcium-channel blocker.

DrugBank - DB01115

• Drug Groups: approved
• Description: Nifedipine has been formulated as both a long- and short-acting 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, nifedipine prevents calcium-dependent myocyte contraction and vasoconstriction. A second proposed mechanism for the drug’s vasodilatory effects involves pH-dependent inhibition of calcium influx via inhibition of smooth muscle carbonic anhydrase. Nifedipine is used to treat hypertension and chronic stable angina.
• Indication: 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).
• Pharmacology: Nifedipine, the prototype of the dihydropyridine class of calcium channel blockers (CCBs), is similar to other dihydropyridines including amlodipine, felodipine, isradipine, and nicardipine. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, nifedipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives nifedipine additional arterial selectivity. At therapeutic sub-toxic concentrations, nifedipine has little effect on cardiac myocytes and conduction cells. By blocking the calcium channels, Nifedipine inhibits the spasm of the coronary artery and dilates the systemic arteries, results in a increase of myocardial oxygen supply and a decrease in systemic blood pressure.
• Toxicity: Symptoms of overdose include dizziness, drowsiness, nausea, severe drop in blood pressure, slurred speech, and weakness. LD₅₀=494 mg/kg (orally in mice); LD₅₀=1022 mg/kg (orally in rats)
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic metabolism via cytochrome P450 system. Predominantly metabolized by CYP3A4, but also by CYP1A2 and CYP2A6 isozymes.
• Absorption: Rapidly and fully absorbed following oral administration.
• Half Life: 2 hours
• Protein Binding: 92-98%
• Elimination: Nifedipine is extensively metabolized to highly water-soluble, inactive metabolites accounting for 60 to 80% of the dose excreted in the urine. The remainder is excreted in the feces in metabolized form, most likely as a result of biliary excretion.
• References: Brown MJ, Palmer CR, Castaigne A, de Leeuw PW, Mancia G, Rosenthal T, Ruilope LM: Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet. 2000 Jul 29;356(9227):366-72. [Pubmed] ; Poole-Wilson PA, Kirwan BA, Voko Z, de Brouwer S, van Dalen FJ, Lubsen J: Safety of nifedipine GITS in stable angina: the ACTION trial. Cardiovasc Drugs Ther. 2006 Feb;20(1):45-54. [Pubmed] ; Odou P, Ferrari N, Barthelemy C, Brique S, Lhermitte M, Vincent A, Libersa C, Robert H: Grapefruit juice-nifedipine interaction: possible involvement of several mechanisms. J Clin Pharm Ther. 2005 Apr;30(2):153-8. [Pubmed] ; Grossman E, Messerli FH, Grodzicki T, Kowey P: Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies? JAMA. 1996 Oct 23-30;276(16):1328-31. [Pubmed] ; Takahashi D, Oyunzul L, Onoue S, Ito Y, Uchida S, Simsek R, Gunduz MG, Safak C, Yamada S: Structure-activity relationships of receptor binding of 1,4-dihydropyridine derivatives. Biol Pharm Bull. 2008 Mar;31(3):473-9. [Pubmed] ; Varon J, Marik PE: Clinical review: the management of hypertensive crises. Crit Care. 2003 Oct;7(5):374-84. Epub 2003 Jul 16. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1808

Research Area: Cardiovascular Disease
Biological Activity:
Nifedipine(Adalat), a potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Nifedipine(Adalat) is a dihydropyridine calcium channel blocker. Its main uses are as an antianginal (especially in Prinzmetal’s angina) and antihypertensive, although a large number of other uses have recently been found for this agent, such as Raynaud’s phenomenon, premature labor, and painful spasms of the esophagus in cancer and tetanus patients. It is also commonly used for the small subset of pulmonary hypertension patients whose symptoms respond to calcium channel blockers. [1]

Sigma Aldrich - N7634

Frequently Asked Questions
Live Chat and Frequently Asked Questions are available for this Product.
Biochem/physiol Actions
L-type Ca2+ channel blocker; induces apoptosis in human glioblastoma cells.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. N7634.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - N457000

Used as an antihypertensive and antianginal. A dihydorpyridine calcium channel blocker.

REFERENCES

• Brown MJ, Palmer CR, Castaigne A, de Leeuw PW, Mancia G, Rosenthal T, Ruilope LM: Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet. 2000 Jul 29;356(9227):366-72. Pubmed
• Poole-Wilson PA, Kirwan BA, Voko Z, de Brouwer S, van Dalen FJ, Lubsen J: Safety of nifedipine GITS in stable angina: the ACTION trial. Cardiovasc Drugs Ther. 2006 Feb;20(1):45-54. Pubmed
• Odou P, Ferrari N, Barthelemy C, Brique S, Lhermitte M, Vincent A, Libersa C, Robert H: Grapefruit juice-nifedipine interaction: possible involvement of several mechanisms. J Clin Pharm Ther. 2005 Apr;30(2):153-8. Pubmed
• Grossman E, Messerli FH, Grodzicki T, Kowey P: Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies? JAMA. 1996 Oct 23-30;276(16):1328-31. Pubmed
• Takahashi D, Oyunzul L, Onoue S, Ito Y, Uchida S, Simsek R, Gunduz MG, Safak C, Yamada S: Structure-activity relationships of receptor binding of 1,4-dihydropyridine derivatives. Biol Pharm Bull. 2008 Mar;31(3):473-9. Pubmed
• Varon J, Marik PE: Clinical review: the management of hypertensive crises. Crit Care. 2003 Oct;7(5):374-84. Epub 2003 Jul 16. Pubmed
• http://en.wikipedia.org/wiki/Nifedipine
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• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, AEC750