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

• ChemBase ID: 284
• Molecular Formular: C20H24N2O6
• Molecular Mass: 388.41436
• Monoisotopic Mass: 388.1634365
• SMILES: O(C(=O)C1=C(NC(=C(C1c1c([N+](=O)[O-])cccc1)C(=O)OC)C)C)CC(C)C
• Canonical SMILES: COC(=O)C1=C(C)NC(=C(C1c1ccccc1[N+](=O)[O-])C(=O)OCC(C)C)C
• InChI: InChI=1S/C20H24N2O6/c1-11(2)10-28-20(24)17-13(4)21-12(3)16(19(23)27-5)18(17)14-8-6-7-9-15(14)22(25)26/h6-9,11,18,21H,10H2,1-5H3
• InChIKey: VKQFCGNPDRICFG-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3-methyl 5-(2-methylpropyl) 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• IUPAC Traditional name: 3-methyl 5-(2-methylpropyl) 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate; nisoldipino; nisoldipine (product)
• Brand Name: Baymycard; Nisocor; Sular; Syscor; Zadipina
• Synonyms: Bay k 5552; Baymycard, Norvasc, Syscor, Zadipina, 1,4-Dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic Acid Methyl 2-Methylpropyl Ester; 3-methyl 5-(2-methylpropyl) 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate; Nisocor; 3-isobutyl 5-methyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate; (±)-Isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(o-nitrophenyl)-3,5-pyridinedicarboxylate; 1,4-Dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-methylpropyl ester; Sular; Nisoldipine; Nisoldipinum [INN-Latin]; Nisoldipino [INN-Spanish]; Nisoldipin; Nisoldipine

Database IDs

• CAS Number: 63675-72-9
• EC Number: 264-407-7
• MDL Number: MFCD00478055
• PubChem SID: 160963747; 46504546
• PubChem CID: 4499

CALCULATED PROPERTIES

JChem

• H Acceptors: 5
• H Donor: 1
• LogD (pH = 5.5): 2.8399477
• LogD (pH = 7.4): 3.056208
• Log P: 3.0597975
• Molar Refractivity: 105.9089 cm^3
• Polarizability: 39.47395 Å^3
• Polar Surface Area: 110.45 Å^2
• Rotatable Bonds: 8
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.63
• LOG S: -4.83
• Solubility (Water): 5.77e-03 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO: >10 mg/mL; Ethanol; Methanol
• Apperance: yellow powder; Yellow Solid
• Melting Point: 147-148°C
• Hydrophobicity(logP): 3.1; 4.582

Safety Information

• Storage Condition: -20°C Freezer
• RTECS: US7975600
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 20/21/22
• Safety Statements: 36
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302-H312
• GHS Precautionary statements: P280
• Storage Temperature: room temp

Pharmacology Properties

• Mechanism of Action: By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum; Calcium channel antagonist; 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 across the myocardial and vascular smooth muscle cell membranes.; The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells,

Product Information

• Purity: ≥98% (HPLC); 95%
• Application(s): Antihypertensive agent; Coronary vasodilator
• Empirical Formula (Hill Notation): C20H24N2O6

DETAILS

DrugBank - DB00401

• Drug Groups: approved
• Description: Nisoldipine is a 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, nisoldipine prevents calcium-dependent smooth muscle contraction and subsequent vasoconstriction. Nisoldipine may be used in alone or in combination with other agents in the management of hypertension.
• Indication: For the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.
• Pharmacology: Nisoldipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nisoldipine is similar to other peripheral vasodilators. Nisoldipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, 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.
• Affected Organisms: Humans and other mammals
• Biotransformation: Pre-systemic metabolism in the gut wall, and this metabolism decreases from the proximal to the distal parts of the intestine. Nisoldipine is highly metabolized; 5 major urinary metabolites have been identified. The major biotransformation pathway appears to be the hydroxylation of the isobutyl ester. A hydroxylated derivative of the side chain, present in plasma at concentrations approximately equal to the parent compound, appears to be the only active metabolite and has about 10% of the activity of the parent compound. Cytochrome P450 enzymes are believed to play a major role in the metabolism of nisoldipine. The particular isoenzyme system responsible for its metabolism has not been identified, but other dihydropyridines are metabolized by cytochrome P450 IIIA4.
• Absorption: Relatively well absorbed into the systemic circulation with 87% of the radiolabeled drug recovered in urine and feces. The absolute bioavailability of nisoldipine is about 5%.
• Half Life: 7-12 hours
• Protein Binding: 99%
• Elimination: Although 60-80% of an oral dose undergoes urinary excretion, only traces of unchanged nisoldipine are found in urine.
• References: Mielcarek J, Grobelny P, Szamburska O: The effect of beta-carotene on the photostability of nisoldipine. Methods Find Exp Clin Pharmacol. 2005 Apr;27(3):167-71. [Pubmed] ; Missan S, Zhabyeyev P, Dyachok O, Jones SE, McDonald TF: Block of cardiac delayed-rectifier and inward-rectifier K+ currents by nisoldipine. Br J Pharmacol. 2003 Nov;140(5):863-70. Epub 2003 Oct 6. [Pubmed] ; Hamilton SF, Houle LM, Thadani U: Rapid-release and coat-core formulations of nisoldipine in treatment of hypertension, angina, and heart failure. Heart Dis. 1999 Nov-Dec;1(5):279-88. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - N0165

Biochem/physiol Actions
L-type (CaV1.2) calcium channel blocker; dihydropyridine-type calcium channel blocker with selectivity for smooth muscle (CaV1.2b) over cardiac muscle (CaV1.2a). Arterial vasodilator and antihypertensive agent.

Toronto Research Chemicals - N489125

Dihydropyridine calcium channel blocker. Antihypertensive and antianginal.

REFERENCES

• Mielcarek J, Grobelny P, Szamburska O: The effect of beta-carotene on the photostability of nisoldipine. Methods Find Exp Clin Pharmacol. 2005 Apr;27(3):167-71. Pubmed
• Missan S, Zhabyeyev P, Dyachok O, Jones SE, McDonald TF: Block of cardiac delayed-rectifier and inward-rectifier K+ currents by nisoldipine. Br J Pharmacol. 2003 Nov;140(5):863-70. Epub 2003 Oct 6. Pubmed
• Hamilton SF, Houle LM, Thadani U: Rapid-release and coat-core formulations of nisoldipine in treatment of hypertension, angina, and heart failure. Heart Dis. 1999 Nov-Dec;1(5):279-88. Pubmed
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