(2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide

• ChemBase编号: 1126
• 分子式: C30H53N3O6
• 平均质量: 551.75832
• 单一同位素质量: 551.39343643
• SMILES: O[C@H]([C@@H](N)C[C@@H](C(C)C)Cc1cc(OCCCOC)c(OC)cc1)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(=O)N
• Canonical SMILES: COCCCOc1cc(ccc1OC)C[C@H](C(C)C)C[C@@H]([C@H](C[C@H](C(=O)NCC(C(=O)N)(C)C)C(C)C)O)N
• InChI: InChI=1S/C30H53N3O6/c1-19(2)22(14-21-10-11-26(38-8)27(15-21)39-13-9-12-37-7)16-24(31)25(34)17-23(20(3)4)28(35)33-18-30(5,6)29(32)36/h10-11,15,19-20,22-25,34H,9,12-14,16-18,31H2,1-8H3,(H2,32,36)(H,33,35)/t22-,23-,24-,25-/m0/s1
• InChIKey: UXOWGYHJODZGMF-QORCZRPOSA-N

名称和登记号

名称

• IUPAC标准名: (2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide
• IUPAC传统名: tekturna; aliskiren
• 商标名: Rasilez; Tekturna
• 别名: Rasilez; aliskiren; SPP 100; Aliskiren; (αS,γS,δS,zS)-δ-Amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-γ-hydroxy-4-methoxy-3-(3-methoxypropoxy)-α,z-bis(1-methylethyl)benzeneoctanamide Hemifumarate; CGP 60536; CGP60536B; Rasilez Hemifumarate; Tekturna Hemifumarate; Aliskiren Hemifumarate

登记号

• CAS号: 173334-57-1; 173334-58-2
• PubChem SID: 160964589; 46507474
• PubChem CID: 5493444

理论计算性质

JChem

• Acid pKa: 14.557217
• 质子受体: 7
• 质子供体: 4
• LogD (pH = 5.5): 0.12925176
• LogD (pH = 7.4): 1.0046214
• Log P: 3.1245122
• 摩尔折射率: 154.3183 cm^3
• 极化性: 61.064808 Å^3
• 极化表面积: 146.13 Å^2
• 可自由旋转的化学键: 19
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 3.87
• LOG S: -5.42
• 溶解度: 2.10e-03 g/l

分子性质

理化性质

• 溶解度: Highly soluble in water (as hemifumarate salt); Methanol; Water
• 外观: White Solid
• 熔点: 96-101°C
• 疏水性(logP): 3.3

安全信息

• 保存条件: Hygroscopic, -20°C Freezer, Under Inert Atmosphere

详细说明

DrugBank - DB01258

• Drug Groups: approved; investigational
• Description: Aliskiren is a renin inhibitor. It was approved by the U.S. Food and Drug Administration in 2007 for the treatment of hypertension.
• Indication: For the treatment of mild to moderate hypertension. It may be used alone or in combination with other antihypertensive agents.
• Pharmacology: Aliskiren is a nonpeptide renin inhibitor marketed under the trade name Tekturna by Novartis.
• Toxicity: The most likely manifestation of overdosage would be hypotension.
• Affected Organisms: Humans and other mammals
• Biotransformation: Approximately 80% of the drug in plasma following oral administration is unchanged. Cytochrome P450 (CYP) 3A4 oxidation produces two major metabolites that account for approximately 5% of the drug in plasma. Aliskiren is eliminated primarily through the biliary/fecal route as unchanged drug and, to a lesser extent, via oxidative metabolism via CYP3A4. Only 0.6% of the oral dose is recovered in urine.
• Absorption: Rapidly absorbed following oral administration. Absolute bioavailability = 2.6%
• Half Life: 24-41 hours
• Protein Binding: 47-51%
• Elimination: About one fourth of the absorbed dose appears in the urine as parent drug.
• References: Gradman AH, Schmieder RE, Lins RL, Nussberger J, Chiang Y, Bedigian MP: Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation. 2005 Mar 1;111(8):1012-8. Epub 2005 Feb 21. [Pubmed] ; Staessen JA, Li Y, Richart T: Oral renin inhibitors. Lancet. 2006 Oct 21;368(9545):1449-56. [Pubmed] ; Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP: Clinical pharmacokinetics and pharmacodynamics of aliskiren. Clin Pharmacokinet. 2008;47(8):515-31. [Pubmed]
• External Links: Wikipedia; Drugs.com

Toronto Research Chemicals - A536001

An orally active, synthetic nonpeptide renin inhibitor. Antihypertensive.

参考文献

• Gradman AH, Schmieder RE, Lins RL, Nussberger J, Chiang Y, Bedigian MP: Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation. 2005 Mar 1;111(8):1012-8. Epub 2005 Feb 21. Pubmed
• Staessen JA, Li Y, Richart T: Oral renin inhibitors. Lancet. 2006 Oct 21;368(9545):1449-56. Pubmed
• Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP: Clinical pharmacokinetics and pharmacodynamics of aliskiren. Clin Pharmacokinet. 2008;47(8):515-31. Pubmed
• Lefevre, G., et al.: J. Immunoassay, 21, 65 (2000)
• Allikments, K., et al.: Curr. Opin. Invest. Drugs, 3, 1479 (2000)
• Wood, J.M., et al.: Biochem. Biophys. Res. Commun., 308, 698 (2000)
• Grandman, A.H., et al.: Circulation, 111, 1012 (2000)