3-methyl 5-propan-2-yl 4-(2,1,3-benzoxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate

• ChemBase编号: 155
• 分子式: C19H21N3O5
• 平均质量: 371.38714
• 单一同位素质量: 371.14812079
• SMILES: O(C(=O)C1=C(NC(=C(C1c1c2nonc2ccc1)C(=O)OC)C)C)C(C)C
• Canonical SMILES: COC(=O)C1=C(C)NC(=C(C1c1cccc2c1non2)C(=O)OC(C)C)C
• InChI: InChI=1S/C19H21N3O5/c1-9(2)26-19(24)15-11(4)20-10(3)14(18(23)25-5)16(15)12-7-6-8-13-17(12)22-27-21-13/h6-9,16,20H,1-5H3
• InChIKey: HMJIYCCIJYRONP-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 3-methyl 5-propan-2-yl 4-(2,1,3-benzoxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• IUPAC传统名: isradipine
• 商标名: Clivoten; DynaCire; DynaCire CR; DynaCirc; Dynacirc CR; Dynacrine; Esradin; Lomir; Prescal; Rebriden
• 别名: 4-(4-Benzofurazanyl)-1,-4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methylethyl ester; Isradipine; (+/-)-Isradipine; Isradipino [Spanish]; Isradipinum [Latin]; Isrodipine; Isradipin; Isradipine; DynaCirc; Prescal; PN-200-110; Clivoten; Esr; 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic Acid Methyl 1-Methylethyl Ester; DynaCirc; Esradin; Lomir

登记号

• CAS号: 75695-93-1
• MDL号: MFCD00153820
• PubChem SID: 160963618; 24724517; 46505034
• PubChem CID: 3784

理论计算性质

JChem

• 质子受体: 5
• 质子供体: 1
• LogD (pH = 5.5): 1.7748289
• LogD (pH = 7.4): 1.995238
• Log P: 1.9989158
• 摩尔折射率: 100.0842 cm^3
• 极化性: 38.38981 Å^3
• 极化表面积: 103.55 Å^2
• 可自由旋转的化学键: 6
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 3.0
• LOG S: -3.21
• 溶解度: 2.28e-01 g/l

分子性质

理化性质

• 溶解度: DMSO: >10 mg/mL; Practically insoluble (< 10 mg/L at 37 °C)
• 外观: yellow solid; Yellow Solid
• 熔点: 166-168°C
• 疏水性(logP): 2.901

安全信息

• 保存条件: -20°C; -20°C Freezer, Under Inert Atmosphere
• 德国WGK号: 3
• 个人保护装置: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• 保存温度: 2-8°C

药理学性质

• 相关基因信息: human ... CACNA2D1(781)

产品相关信息

• 纯度: ≥98% (HPLC)
• 成盐信息: Free Base
• 简要说明: Store under nitrogen
• Empirical Formula (Hill Notation): C19H21N3O5

详细说明

DrugBank - DB00270

• Drug Groups: approved
• Description: Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. It is structurally related to felodipine, nifedipine, and nimodipine and is the most potent calcium-channel blocking agent of the DHP class. Isradipine binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and arterial smooth muscle cells. It exhibits greater selectivity towards arterial smooth muscle cells owing to alternative splicing of the alpha-1 subunit of the channel and increased prevalence of inactive channels in smooth muscle cells. Isradipine may be used to treat mild to moderate essential hypertension.
• Indication: For the management of mild to moderate essential hypertension. It may be used alone or concurrently with thiazide-type diuretics.
• Pharmacology: Isradipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of isradipine result in an overall decrease in blood pressure.
• Toxicity: Symptoms of overdose include lethargy, sinus tachycardia, and transient hypotension. Significant lethality was observed in mice given oral doses of over 200 mg/kg and rabbits given about 50 mg/kg of isradipine. Rats tolerated doses of over 2000 mg/kg without effects on survival.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Completely metabolized prior to excretion and no unchanged drug is detected in the urine.
• Absorption: Isradipine is 90%-95% absorbed and is subject to extensive first-pass metabolism, resulting in a bioavailability of about 15%-24%.
• Half Life: 8 hours
• Protein Binding: 95%
• Elimination: Approximately 60% to 65% of an administered dose is excreted in the urine and 25% to 30% in the feces.
• References: Fletcher H, Roberts G, Mullings A, Forrester T: An open trial comparing isradipine with hydralazine and methyl dopa in the treatment of patients with severe pre-eclampsia. J Obstet Gynaecol. 1999 May;19(3):235-8. [Pubmed] ; Ganz M, Mokabberi R, Sica DA: Comparison of blood pressure control with amlodipine and controlled-release isradipine: an open-label, drug substitution study. J Clin Hypertens (Greenwich). 2005 Apr;7(4 Suppl 1):27-31. [Pubmed] ; Hattori T, Wang PL: Calcium antagonist isradipine-induced calcium influx through nonselective cation channels in human gingival fibroblasts. Eur J Med Res. 2006 Mar 27;11(3):93-6. [Pubmed] ; Johnson BA, Roache JD, Ait-Daoud N, Wallace C, Wells L, Dawes M, Wang Y: Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects. Int J Neuropsychopharmacol. 2005 Jun;8(2):203-13. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1662

Research Area: Cardiovascular Disease
Biological Activity:
Isradipine(Dynacirc) is a calcium channel blocker with an IC50 of 34±8 μM.It is usually prescribed for the treatment of high blood pressure in order to reduce the risk of stroke and heart attack. [1] the interactive effects of isradipine and blockers or enhancers of nonselective cation channels (NSCCs) and Na+/Ca2+ exchangers (NCXs). Normal human gingival fibroblast Gin-1 cells were used. The [Ca2+]i was measured with the Ca2+-sensitive fluorescent dye fura-2/AM. Changes in the fluorescence intensity of fura-2 in the cells were recorded with a video-imaging analysis system. Ca2+ antagonists (nifedipine, verapamil, and diltiazem in the concentration range of 1 to 20 μM) other than isradipine also raised the [Ca2+]i. [2] 

Sigma Aldrich - I6658

Biochem/physiol Actions
L-type calcium channel blocker (also referred to as dihydropyridine-type calcium channel blocker); antihypertensive.

Toronto Research Chemicals - I925000

Dihydropyridine calcium channel blocker. Antihypertensive; antianginal.

参考文献

• Fletcher H, Roberts G, Mullings A, Forrester T: An open trial comparing isradipine with hydralazine and methyl dopa in the treatment of patients with severe pre-eclampsia. J Obstet Gynaecol. 1999 May;19(3):235-8. Pubmed
• Ganz M, Mokabberi R, Sica DA: Comparison of blood pressure control with amlodipine and controlled-release isradipine: an open-label, drug substitution study. J Clin Hypertens (Greenwich). 2005 Apr;7(4 Suppl 1):27-31. Pubmed
• Hattori T, Wang PL: Calcium antagonist isradipine-induced calcium influx through nonselective cation channels in human gingival fibroblasts. Eur J Med Res. 2006 Mar 27;11(3):93-6. Pubmed
• Johnson BA, Roache JD, Ait-Daoud N, Wallace C, Wells L, Dawes M, Wang Y: Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects. Int J Neuropsychopharmacol. 2005 Jun;8(2):203-13. Pubmed
• Hattori T et al. Eur J Med Res. 2006 Mar 27;11(3)
• Nelson, E.B., et al.: Clin. Pharmacol. Ther., 40, 694 (1986)
• Hof, R.P., et al.: J. Cardiovasc. Pharmacol., 8, 221 (1986)