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114798-26-4 分子结构
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[2-butyl-4-chloro-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-imidazol-5-yl]methanol

ChemBase编号:560
分子式:C22H23ClN6O
平均质量:422.91062
单一同位素质量:422.16218707
SMILES和InChIs

SMILES:
Clc1nc(n(Cc2ccc(cc2)c2c(cccc2)c2n[nH]nn2)c1CO)CCCC
Canonical SMILES:
CCCCc1nc(c(n1Cc1ccc(cc1)c1ccccc1c1n[nH]nn1)CO)Cl
InChI:
InChI=1S/C22H23ClN6O/c1-2-3-8-20-24-21(23)19(14-30)29(20)13-15-9-11-16(12-10-15)17-6-4-5-7-18(17)22-25-27-28-26-22/h4-7,9-12,30H,2-3,8,13-14H2,1H3,(H,25,26,27,28)
InChIKey:
PSIFNNKUMBGKDQ-UHFFFAOYSA-N

引用这个纪录

CBID:560 http://www.chembase.cn/molecule-560.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
[2-butyl-4-chloro-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-imidazol-5-yl]methanol
IUPAC传统名
losartan
商标名
Cozaar
Hyzaar
Lacidipine
Lortaan
别名
DUP 89
Losartan Potassium
Losartan
CAS号
114798-26-4
PubChem SID
160964023
46506538
PubChem CID
3961

数据来源

数据来源

所有数据来源 商品来源 非商品来源
数据来源 数据ID
DrugBank DB00678 external link
PubChem 3961 external link
数据来源 数据ID 价格

理论计算性质

理论计算性质

JChem ALOGPS 2.1
Acid pKa 7.399772  质子受体
质子供体 LogD (pH = 5.5) 5.0622497 
LogD (pH = 7.4) 4.7956624  Log P 5.084907 
摩尔折射率 131.8496 cm3 极化性 46.464104 Å3
极化表面积 92.51 Å2 可自由旋转的化学键
里宾斯基五规则 false 
Log P 4.5  LOG S -4.95 
溶解度 4.70e-03 g/l 

分子性质

分子性质

理化性质 生物活性(PubChem)
溶解度
0.82 mg/L expand 查看数据来源
疏水性(logP)
6.1 expand 查看数据来源

详细说明

详细说明

DrugBank DrugBank
DrugBank -  DB00678 external link
Item Information
Drug Groups approved
Description Losartan is an angiotensin-receptor blocker (ARB) that may be used alone or with other agents to treat hypertension. Losartan and its longer acting metabolite, E-3174, lower blood pressure by antagonizing the renin-angiotensin-aldosterone system (RAAS); they compete 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. Losartan 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 systolic dysfunction, myocardial infarction, coronary artery disease, and heart failure.
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 Losartan is the first of a class of antihypertensive agents called angiotensin II receptor blockers (ARBs). Losartan and its longer acting active metabolite, E-3174, are specific and selective type-1 angiotensin II receptor (AT1) antagonists which block 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.
Toxicity Hypotension and tachycardia; Bradycardia could occur from parasympathetic (vagal) stimulation, LD50= 1000 mg/kg (orally in rat)
Affected Organisms
Humans and other mammals
Biotransformation Hepatic. Losartan is metabolized to a 5-carboxylic acid derivative (E-3174) via an aldehyde intermediate (E-3179) primarily by cytochrome P450 (CYP) 2C9 and CYP3A4. E-3174 is an active metabolite with 10- to 40-fold higher potency than its parent compound, losartan. Approxiamtely 14% of losartan is converted to E-3174; however, the AUC of E-3174 was found to be 4- to 8-fold higher than losartan and E-3174 is considered the main contributor to the pharmacologic effects of this medication.
Absorption Well absorbed, the systemic bioavailability of losartan is approximately 33%
Half Life The terminal t1/2 of losartan is 2 hours and that of E-3174 is 6-9 hours.
Protein Binding 99.7%, primarily to albumin
Elimination After single doses of losartan administered orally, about 4% of the dose is excreted unchanged in the urine and about 6% is excreted in urine as active metabolite. Biliary excretion contributes to the elimination of losartan and its metabolites.
Distribution * 34 L [losartan]
* 12 L [active metabolite]
Clearance * 600 mL/min [Healthy volunteers after IV administration]
* Renal cl=56 +/- 23 mL/min [Hypertensive adults given 50?mg once daily for 7 days]
* Renal cl=53 +/- 33 mL/min [Hypertensive children (6-16 years old) given 0.7 mg/kg once daily for 7 days]
References
Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H: Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002 Mar 23;359(9311):995-1003. [Pubmed]
Guo ZX, Qiu MC: [Losartan downregulates the expression of transforming growth factor beta type I and type II receptors in kidney of diabetic rat] Zhonghua Nei Ke Za Zhi. 2003 Jun;42(6):403-8. [Pubmed]
Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC: Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006 Apr 7;312(5770):117-21. [Pubmed]
Bader, M. (2004). Renin-angiotensin-aldosterone system. In S. Offermanns, & W. Rosenthal (Eds.). _Encyclopedic reference of molecular pharmacology_ (pp. 810-814). Berlin, Germany: Springer.
Sica, D.A., Gehr, T.W.B., & Ghosh, S. (2005). Clinical pharmacokinetics of losartan. _Clinical Pharmacokinetics, 44_(8), 797-814. "PMID: 16029066":http://www.ncbi.nlm.nih.gov/pubmed/16029066
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

参考文献

参考文献

供应商提供 Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • Stanfield, C.L., & Germann, W.J. (2008). _Principles of human physiology_ (3 ^rd^ ed.). San Francisco, CA: Pearson Education, Inc.
  • Guo ZX, Qiu MC: [Losartan downregulates the expression of transforming growth factor beta type I and type II receptors in kidney of diabetic rat] Zhonghua Nei Ke Za Zhi. 2003 Jun;42(6):403-8. Pubmed
  • Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H: Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002 Mar 23;359(9311):995-1003. Pubmed
  • Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC: Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006 Apr 7;312(5770):117-21. Pubmed
  • Bader, M. (2004). Renin-angiotensin-aldosterone system. In S. Offermanns, & W. Rosenthal (Eds.). _Encyclopedic reference of molecular pharmacology_ (pp. 810-814). Berlin, Germany: Springer.
  • Sica, D.A., Gehr, T.W.B., & Ghosh, S. (2005). Clinical pharmacokinetics of losartan. _Clinical Pharmacokinetics, 44_(8), 797-814. "PMID: 16029066":http://www.ncbi.nlm.nih.gov/pubmed/16029066
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专利

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