(2S)-3-methyl-2-[N-({4-[2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)pentanamido]butanoic acid

• ChemBase编号: 62
• 分子式: C24H29N5O3
• 平均质量: 435.51876
• 单一同位素质量: 435.22703981
• SMILES: OC(=O)[C@@H](N(Cc1ccc(cc1)c1c(cccc1)c1n[nH]nn1)C(=O)CCCC)C(C)C
• Canonical SMILES: CCCCC(=O)N([C@H](C(=O)O)C(C)C)Cc1ccc(cc1)c1ccccc1c1n[nH]nn1
• InChI: InChI=1S/C24H29N5O3/c1-4-5-10-21(30)29(22(16(2)3)24(31)32)15-17-11-13-18(14-12-17)19-8-6-7-9-20(19)23-25-27-28-26-23/h6-9,11-14,16,22H,4-5,10,15H2,1-3H3,(H,31,32)(H,25,26,27,28)/t22-/m0/s1
• InChIKey: ACWBQPMHZXGDFX-QFIPXVFZSA-N

名称和登记号

名称

• IUPAC标准名: (2S)-3-methyl-2-[N-({4-[2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)pentanamido]butanoic acid; (2S)-3-methyl-2-[N-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)pentanamido]butanoic acid
• IUPAC传统名: (2S)-3-methyl-2-[N-({4-[2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)pentanamido]butanoic acid; diovan; valsartan
• 商标名: Diovan; Valsarran
• 别名: Valtan; L-Valsartan; (S)-2-(N-((2'-(1H-Tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid; N-(1-Oxopentyl)-N-[[2′-(2H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-L-valine; Valsartan; valsartan; Valsartan; Diovan

登记号

• CAS号: 137862-53-4
• MDL号: MFCD00865840
• PubChem SID: 46509000; 160963525
• PubChem CID: 60846

理论计算性质

JChem

• Acid pKa: 4.3663416
• 质子受体: 6
• 质子供体: 2
• LogD (pH = 5.5): 4.1015096
• LogD (pH = 7.4): 2.052606
• Log P: 5.269379
• 摩尔折射率: 134.7733 cm^3
• 极化性: 48.579018 Å^3
• 极化表面积: 112.07 Å^2
• 可自由旋转的化学键: 10
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 3.68
• LOG S: -4.27
• 溶解度: 2.34e-02 g/l

分子性质

理化性质

• 溶解度: DMSO: ≥20 mg/mL
• 外观: white to tan powder
• 比旋光度: [α]/D -55 to -70°, c = 1 in methanol
• 疏水性(logP): 5.8

安全信息

• 保存条件: -20°C; desiccated
• 保存注意事项: IRRITANT
• TSCA收录: false
• 保存温度: 2-8°C

药理学性质

• 作用靶点: Angiotensin recep
• 生物活性机理: Angiotensin 2 receptor antagonist

产品相关信息

• 纯度: ≥98% (HPLC); 95+%
• 成盐信息: Free Base
• 应用领域: Antihypertensive agent
• Empirical Formula (Hill Notation): C24H29N5O3

详细说明

DrugBank - DB00177

• Drug Groups: approved; investigational
• Description: Valsartan is an angiotensin-receptor blocker (ARB) that may be used to treat a variety of cardiac conditions including hypertension, diabetic nephropathy and heart failure. Valsartan lowers blood pressure by antagonizing the renin-angiotensin-aldosterone system (RAAS); it competes with angiotensin II for binding to the type-1 angiotensin II receptor (AT1) subtype and prevents the blood pressure increasing effects of angiotensin II. Unlike angiotensin-converting enzyme (ACE) inhibitors, ARBs do not have the adverse effect of dry cough. Valsartan may be used to treat hypertension, isolated systolic hypertension, left ventricular hypertrophy and diabetic nephropathy. It may also be used as an alternative agent for the treatment of heart failure, systolic dysfunction, myocardial infarction and coronary artery disease.
• Indication: May be used as a first line agent to treat uncomplicated hypertension, isolated systolic hypertension and left ventricular hypertrophy. May be used as a first line agent to delay progression of diabetic nephropathy. Losartan may be also used as a second line agent in the treatment of congestive heart failure, systolic dysfunction, myocardial infarction and coronary artery disease in those intolerant of ACE inhibitors.
• Pharmacology: Valsartan belongs to a class of antihypertensive agents called angiotensin II receptor blockers (ARBs). Valsartan is a specific and selective type-1 angiotensin II receptor (AT1) antagonist which blocks the blood pressure increasing effects angiotensin II via the renin-angiotensin-aldosterone system (RAAS). RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from granular cells of the juxtaglomerular apparatus in the kidneys. Renin cleaves circulating angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing total peripheral resistance, increasing sodium and water reabsorption in the kidneys via aldosterone secretion, and altering cardiovascular structure. Angiotensin II binds to two receptors: AT1 and type-2 angiotensin II receptor (AT2). AT1 is a G-protein coupled receptor (GPCR) that mediates the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Studies performed in recent years suggest that AT2 antagonizes AT1-mediated effects and directly affects long-term blood pressure control by inducing vasorelaxation and increasing urinary sodium excretion. Angiotensin receptor blockers (ARBs) are non-peptide competitive inhibitors of AT1. ARBs block the ability of angiotensin II to stimulate pressor and cell proliferative effects. Unlike ACE inhibitors, ARBs do not affect bradykinin-induced vasodilation. The overall effect of ARBs is a decrease in blood pressure.
• Affected Organisms: Humans and other mammals
• Biotransformation: Valsartan is excreted largely as unchanged drug (80%) and is minimally metabolized in humans. The primary circulating metabolite, 4-OH-valsartan, is pharmacologically inactive and produced CYP2C9. 4-OH-valsartan accounts for approximately 9% of the circulating dose of valsartan. Although valsartan is metabolized by CYP2C9, CYP-mediated drug-drug interactions between valsartan and other drugs is unlikely.
• Absorption: Absolute bioavailability = 23% with high variability
• Half Life: The initial phase t_{1/2 α} is < 1 hour while the terminal phase t_{1/2 β} is 5-9 hours.
• Protein Binding: 94 - 97% bound to serum proteins, primarily serum albumin
• Elimination: 83% of absorbed valsartan is excreted in feces and 13% is excreted in urine, primarily as unchanged drug
• Distribution: * 17 L (low tissue distribution)
• Clearance: * 2 L/h [IV administration]; * 4.5 L/h [heart Failure patients receiving oral administration 40 to 160 mg twice a day]
• References: Bader, M. (2004). Renin-angiotensin-aldosterone system. In S. Offermanns, & W. Rosenthal (Eds.). _Encyclopedic reference of molecular pharmacology_ (pp. 810-814). Berlin, Germany: Springer.; Diovan. (2009). [Electronic version]. e-CPS. Retrieved December 28, 2009.; Stanfield, C.L., & Germann, W.J. (2008). _Principles of human physiology_ (3 ^rd^ ed.). San Francisco, CA: Pearson Education, Inc.
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1894

Research Area: Cardiovascular Disease
Biological Activity:
Valsartan (Diovan) is an angiotensin II receptor antagonist with IC50 of ranging from 39.5 to116 µM. By blocking the action of angiotensin, valsartan dilates blood vessels and reduces blood pressure. In the Value trial, the angiotensin II receptor blocker valsartan produced a statistically significant 19% (p=0.02) relative increase in the prespecified secondary end point of myocardial infarction (fatal and non-fatal) compared with amlodipine. The CHARM-alternative trial showed a significant +52% (p=0.025) increase in myocardial infarction with candesartan (versus placebo) despite a reduction in blood pressure. [1]

参考文献

• Diovan. (2009). [Electronic version]. e-CPS. Retrieved December 28, 2009.
• Stanfield, C.L., & Germann, W.J. (2008). _Principles of human physiology_ (3 ^rd^ ed.). San Francisco, CA: Pearson Education, Inc.
• Bader, M. (2004). Renin-angiotensin-aldosterone system. In S. Offermanns, & W. Rosenthal (Eds.). _Encyclopedic reference of molecular pharmacology_ (pp. 810-814). Berlin, Germany: Springer.
• http://en.wikipedia.org/wiki/Valsartan
• Eur. Pat., 1991, Ciba-Geigy, 443 983; CA, 116, 151772t, (synth, pharmacol)
• Criscione, L. et al., Br. J. Pharmacol., 1993, 110, 761, (pharmacol)
• Wood, J.M. et al., Hypertension (Dallas), 1993, 21, 1056, (pharmacol)
• Buhlmayer, P. et al., Bioorg. Med. Chem. Lett., 1994, 4, 29, (synth)
• Markham, A. et al., Drugs, 1997, 54, 299-311, (rev)
• Langley, H.D. et al., Drugs, 1999, 57, 751-755, (rev)
• Martindale, The Extra Pharmacopoeia, 32nd edn., Pharmaceutical Press, 1999, 960