3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate

• ChemBase编号: 265
• 分子式: C20H25ClN2O5
• 平均质量: 408.8759
• 单一同位素质量: 408.14519959
• SMILES: Clc1c(C2C(=C(NC(=C2C(=O)OC)C)COCCN)C(=O)OCC)cccc1
• Canonical SMILES: NCCOCC1=C(C(=O)OCC)C(C(=C(N1)C)C(=O)OC)c1ccccc1Cl
• InChI: InChI=1S/C20H25ClN2O5/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21/h5-8,17,23H,4,9-11,22H2,1-3H3
• InChIKey: HTIQEAQVCYTUBX-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
• IUPAC传统名: amlodipine
• 商标名: Amlocard; Amlodis; Amvaz; Coroval; Lipinox; Norvasc; Lotrel
• 别名: 2-[(2-Aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl)-6-methyl-1,4-dihydropyridine; (R,S)-Amlodipine; Amlopres; Intervask; Pelmec; UK-48340; Istin; Norvasc; Caduet; Amlodipine Benzenesulfonate; Amlodipine Besilate; Amlodipine Besylate; Amlodipine Free Base; Amlodipino [Spanish]; Amlodipinum [Latin]; Amlodipine

登记号

• CAS号: 88150-42-9
• PubChem SID: 46507214; 160963728
• PubChem CID: 2162

理论计算性质

JChem

• 质子受体: 5
• 质子供体: 2
• LogD (pH = 5.5): -1.366646
• LogD (pH = 7.4): -0.37164375
• Log P: 1.6355954
• 摩尔折射率: 108.6381 cm^3
• 极化性: 41.695133 Å^3
• 极化表面积: 99.88 Å^2
• 可自由旋转的化学键: 10
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 2.22
• LOG S: -4.74
• 溶解度: 7.40e-03 g/l

分子性质

理化性质

• 溶解度: 75.3 mg/L; Acetone; Chloroform; Ethyl Acetate; Methanol
• 外观: Off-White to Pale Yellow Solid
• 熔点: 133-135°C
• 疏水性(logP): 1.9

安全信息

• 保存条件: -20°C; -20°C Freezer

产品相关信息

• 成盐信息: Free Base

详细说明

DrugBank - DB00381

• Drug Groups: approved
• Description: Amlodipine is a long-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, amlodipine 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. Some studies have shown that amlodipine also exerts inhibitory effects on voltage-gated N-type calcium channels. N-type calcium channels located in the central nervous system may be involved in nociceptive signaling and pain sensation. Amlodipine is used to treat hypertension and chronic stable angina.
• Indication: For the treatment of hypertension and chronic stable angina.
• Pharmacology: Amlodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that DHP CCBs target L-type calcium channels, the major channel in muscle cells that mediate contraction; however, some studies have indicated that amlodipine also binds to and inhibits N-type calcium channels (see references in Targets section). Similar to other DHP CCBs, amlodipine binds directly to inactive L-type 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 amlodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, amlodipine has little effect on cardiac myocytes and conduction cells.
• Toxicity: Gross overdosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to an including shock with fatal outcome have been reported.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Metabolized extensively (90%) to inactive metabolites via the cytochrome P450 3A4 isozyme.
• Absorption: Amlodipine is slowly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached 6-12 hour following oral administration. Its estimated bioavailability is 64-90%. Absorption is not affected by food.
• Half Life: 30-50 hours
• Protein Binding: 97.5%
• Elimination: Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine.
• References: Nayler WG, Gu XH: The unique binding properties of amlodipine: a long-acting calcium antagonist. J Hum Hypertens. 1991 Aug;5 Suppl 1:55-9. [Pubmed] ; van Zwieten PA: Amlodipine: an overview of its pharmacodynamic and pharmacokinetic properties. Clin Cardiol. 1994 Sep;17(9 Suppl 3):III3-6. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1905

Research Area: Cardiovascular Disease
Biological Activity:
Amlodipine(Norvasc) is a long-acting calcium channel blocker with an IC50 of 1.9 nM used as an anti-hypertensive and in the treatment of angina. Like other calcium channel blockers, amlodipine acts by relaxing the smooth muscle in the arterial wall, decreasing total peripheral resistance and hence reducing blood pressure; in angina it increases blood flow to the heart muscle. [1][2]

Toronto Research Chemicals - A633495

A dihydropyridine calcium channel blocker; activity resides mainly in the (-)-isomer.

参考文献

• Nayler WG, Gu XH: The unique binding properties of amlodipine: a long-acting calcium antagonist. J Hum Hypertens. 1991 Aug;5 Suppl 1:55-9. Pubmed
• van Zwieten PA: Amlodipine: an overview of its pharmacodynamic and pharmacokinetic properties. Clin Cardiol. 1994 Sep;17(9 Suppl 3):III3-6. Pubmed
• Burges RA et al. J Cardiovasc Pharmacol. 1987 Jan; 9(1):110-9.
• Arrowsmith, J.E., et al.: J. Med. Chem., 29, 1696 (1986)
• Burges, R.A., et al.: J. Cardiovasc. Pharmacol., 9, 110 (1986)
• Haria, M., et al.: Drugs, 50, 560 (1986)