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139481-59-7 molecular structure
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2-ethoxy-1-({4-[2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-1,3-benzodiazole-7-carboxylic acid

ChemBase ID: 675
Molecular Formular: C24H20N6O3
Molecular Mass: 440.454
Monoisotopic Mass: 440.15968853
SMILES and InChIs

SMILES:
O(c1n(Cc2ccc(cc2)c2c(cccc2)c2n[nH]nn2)c2c(n1)cccc2C(=O)O)CC
Canonical SMILES:
CCOc1nc2c(n1Cc1ccc(cc1)c1ccccc1c1n[nH]nn1)c(ccc2)C(=O)O
InChI:
InChI=1S/C24H20N6O3/c1-2-33-24-25-20-9-5-8-19(23(31)32)21(20)30(24)14-15-10-12-16(13-11-15)17-6-3-4-7-18(17)22-26-28-29-27-22/h3-13H,2,14H2,1H3,(H,31,32)(H,26,27,28,29)
InChIKey:
HTQMVQVXFRQIKW-UHFFFAOYSA-N

Cite this record

CBID:675 http://www.chembase.cn/molecule-675.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
2-ethoxy-1-({4-[2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-1,3-benzodiazole-7-carboxylic acid
2-ethoxy-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-1,3-benzodiazole-7-carboxylic acid
IUPAC Traditional name
candesartan
blopress
atacand
Brand Name
Atacand
Blopress
Amias
Ratacand
Synonyms
1-((2'-(1H-Tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylic acid
2-Ethoxy-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-benzimidazole-7-carboxylic Acid
3-[[2'-(1H-Tetrazol-5-yl)biphenyl-4-yl]methyl]-2-ethoxy-3H-benzimidazole-4-carboxylic Acid
CV-11974
Candesartan M1
Candesartan cilexetil
Candesartan
Atacand
Blopress
Amias
Ratacand
2-ethoxy-3-((4-(2-(1h-tetrazol-5-yl)phenyl)phenyl)methyl)-3h-benzoimidazole-4-carboxylic acid
CAS Number
139481-59-7
MDL Number
MFCD00864463
PubChem SID
160964138
46508342
PubChem CID
2541

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
Acid pKa 3.4423606  H Acceptors
H Donor LogD (pH = 5.5) 1.5652357 
LogD (pH = 7.4) -0.2964591  Log P 4.511789 
Molar Refractivity 134.9175 cm3 Polarizability 48.98611 Å3
Polar Surface Area 118.81 Å2 Rotatable Bonds
Lipinski's Rule of Five true 
Log P 4.02  LOG S -4.76 
Solubility (Water) 7.71e-03 g/l 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
Cancer expand Show data source
Ethyl Acetate expand Show data source
Methanol expand Show data source
Apperance
Off-White to Pale Yellow Solid expand Show data source
Melting Point
163-165°C (dec.) expand Show data source
Hydrophobicity(logP)
6.1 expand Show data source
Storage Condition
-20°C expand Show data source
-20°C Freezer expand Show data source
Storage Warning
IRRITANT expand Show data source
MSDS Link
Download expand Show data source
Download expand Show data source
TSCA Listed
false expand Show data source
Target
Angiotensin receptor expand Show data source
Purity
95+% expand Show data source
97% expand Show data source
98% expand Show data source
Salt Data
Free Base expand Show data source
Certificate of Analysis
Download expand Show data source

DETAILS

DETAILS

DrugBank DrugBank Selleck Chemicals Selleck Chemicals TRC TRC
DrugBank - DB00796 external link
Item Information
Drug Groups approved
Description Candesartan is an angiotensin-receptor blocker (ARB) that may be used alone or with other agents to treat hypertension. It is administered orally as the prodrug, candesartan cilexetil, which is rapidly converted to its active metabolite, candesartan, during absorption in the gastrointestinal tract. Candesartan 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. Candesartan 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. Candesartan 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 Candesartan cilexetil is an ARB prodrug that is rapidly converted to candesartan, its active metabolite, during absorption from the gastrointestinal tract. Candesartan confers blood pressure lowering effects by antagonizing the hypertensive effects of angiotensin II via the 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: type-1 angiotensin II receptor (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 No lethality was observed in acute toxicity studies in mice, rats and dogs given single oral doses of up to 2000 mg/kg of candesartan cilexetil or in rats given single oral doses of up to 2000 mg/kg of candesartan cilexetil in combination with 1000 mg/kg of hydrochlorothiazide. In mice given single oral doses of the primary metabolite, candesartan, the minimum lethal dose was greater than 1000 mg/kg but less than 2000 mg/kg.
Affected Organisms
Humans and other mammals
Biotransformation The prodrug candesartan cilexetil undergoes rapid and complete ester hydrolysis in the intestinal wall to form the active drug, candesartan. Elimination of candesartan is primarily as unchanged drug in the urine and, by the biliary route, in the feces. Minor hepatic metabolism of candesartan (<20%)occurs by O-deethylation via cytochrome P450 2C9 to form an inactive metabolite. Candesartan undergoes N-glucuronidation in the tetrazole ring by uridine diphosphate glucuronosyltransferase 1A3 (UGT1A3). O-glucuronidation may also occur. 75% of candesartan is excreted as unchanged drug in urine and feces.
Absorption Following administration of the candesartan cilexetil prodrug, the absolute bioavailability of candesartan was estimated to be 15%. Food with a high fat content has no affect on the bioavailability of candesartan from candesartan cilexetil.
Half Life Approximately 9 hours.
Protein Binding Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells.
Elimination When candesartan is administered orally, about 26% of the dose is excreted unchanged in urine. Candesartan is mainly excreted unchanged in urine and feces (via bile).
Distribution * 0.13 L/kg
Clearance * 0.37 mL/min/kg
References
Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S: Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003 Sep 6;362(9386):759-66. [Pubmed]
Mendis B, Page SR: Candesartan: widening indications for this angiotensin II receptor blocker? Expert Opin Pharmacother. 2009 Aug;10(12):1995-2007. [Pubmed]
Baguet JP, Barone-Rochette G, Neuder Y: Candesartan cilexetil in the treatment of chronic heart failure. Vasc Health Risk Manag. 2009;5(1):257-64. Epub 2009 Apr 8. [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.
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 - S1578 external link
Research Area: Cardiovascular Disease
Biological Activity:
Candesartan (Atacand) is an angiotensin II receptor antagonist with an IC50 of 15 µg/kg.It reduced the risk of developing hypertension by nearly two-thirds during this period. In the last two years of the study, all participants were switched to placebo. By the end of the study, candesartan had significantly reduced the risk of hypertension, by more than 15%. [1][2]
Toronto Research Chemicals - C175575 external link
An angiotensin II type-1 receptor antagonist. Used in treatment of congestive heart failure. Antihypertensive.

REFERENCES

REFERENCES

From Suppliers Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • • Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S: Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003 Sep 6;362(9386):759-66. Pubmed
  • • Mendis B, Page SR: Candesartan: widening indications for this angiotensin II receptor blocker? Expert Opin Pharmacother. 2009 Aug;10(12):1995-2007. Pubmed
  • • Baguet JP, Barone-Rochette G, Neuder Y: Candesartan cilexetil in the treatment of chronic heart failure. Vasc Health Risk Manag. 2009;5(1):257-64. Epub 2009 Apr 8. Pubmed
  • • 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/Candesartan
  • • Kaur, N., et al.: Bioorg. Med. Chem., 16, 10210 (2008)
  • • Funao, K., et al.: Mol. Med. Rep., 2, 193 (2008)
  • • Yoshikawa, M., et al.: J. Cardiovas. Pharmacol., 53, 179 (2008)
  • • Palaniyappan, A., et al.: Mol. Cell. Biochem., 321, 9 (2008)
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PATENTS

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