4-({2-butyl-5-[(1Z)-2-carboxy-2-(thiophen-2-ylmethyl)eth-1-en-1-yl]-1H-imidazol-1-yl}methyl)benzoic acid

• ChemBase ID: 754
• Molecular Formular: C23H24N2O4S
• Molecular Mass: 424.51266
• Monoisotopic Mass: 424.14567826
• SMILES: s1c(CC(=Cc2n(c(nc2)CCCC)Cc2ccc(cc2)C(=O)O)C(=O)O)ccc1
• Canonical SMILES: CCCCc1ncc(n1Cc1ccc(cc1)C(=O)O)C=C(C(=O)O)Cc1cccs1
• InChI: InChI=1S/C23H24N2O4S/c1-2-3-6-21-24-14-19(12-18(23(28)29)13-20-5-4-11-30-20)25(21)15-16-7-9-17(10-8-16)22(26)27/h4-5,7-12,14H,2-3,6,13,15H2,1H3,(H,26,27)(H,28,29)
• InChIKey: OROAFUQRIXKEMV-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-({2-butyl-5-[(1Z)-2-carboxy-2-(thiophen-2-ylmethyl)eth-1-en-1-yl]-1H-imidazol-1-yl}methyl)benzoic acid; 4-({2-butyl-5-[(1E)-2-carboxy-2-(thiophen-2-ylmethyl)eth-1-en-1-yl]-1H-imidazol-1-yl}methyl)benzoic acid; 4-({2-butyl-5-[2-carboxy-2-(thiophen-2-ylmethyl)eth-1-en-1-yl]-1H-imidazol-1-yl}methyl)benzoic acid
• IUPAC Traditional name: eprosartan; teveten; 4-({2-butyl-5-[(1E)-2-carboxy-2-(thiophen-2-ylmethyl)eth-1-en-1-yl]-1H-imidazol-1-yl}methyl)benzoic acid
• Brand Name: Teveten
• Synonyms: (αZ)-α-[[2-Butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methylene]-2-thiophenepropanoic Acid; (Z)-α-[[2-Butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methylene]-2-thiophenepropanoic Acid; SB 206328; (Z)-Eprosartan; (αE)-α-[[2-Butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methylene]-2-thiophenepropanoic Acid; (E)-2-Butyl-1-(p-carboxybenzyl)-α-2-thenylimidazole-5-acrylic Acid; Navixen; SKB 108566; SKF 108566; Teveten; Eprosartan; Eprosartan

Database IDs

• CAS Number: 148674-39-9; 133040-01-4
• PubChem SID: 160964217
• PubChem CID: 60879

CALCULATED PROPERTIES

JChem

• Acid pKa: 3.6324818
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): 2.6257877
• LogD (pH = 7.4): 0.3021144
• Log P: 3.7972305
• Molar Refractivity: 117.0243 cm^3
• Polarizability: 44.08464 Å^3
• Polar Surface Area: 92.42 Å^2
• Rotatable Bonds: 10
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.57
• LOG S: -4.69
• Solubility (Water): 8.66e-03 g/l

PROPERTIES

Physical Property

• Solubility: Insoluble (mesylate form); Methanol
• Apperance: Light-Yellow Solid
• Melting Point: >246°C (dec.)
• Hydrophobicity(logP): 3.9

Safety Information

• Storage Condition: -20°C Freezer

Pharmacology Properties

• Mechanism of Action: Angiotensin II AT 1 -receptor antagonist

Product Information

• Application(s): Antihypertensive agent

DETAILS

DrugBank - DB00876

• Drug Groups: approved
• Description: Eprosartan is an angiotensin II receptor antagonist used for the treatment of high blood pressure. It acts on the renin-angiotensin system in two ways to decrease total peripheral resistance. First, it blocks the binding of angiotensin II to AT1 receptors in vascular smooth muscle, causing vascular dilatation. Second, it inhibits sympathetic norepinephrine production, further reducing blood pressure.
• Indication: For the management of hypertension alone or in combination with other classes of antihypertensive agents. Also used as a first-line agent in the treatment of diabetic nephropathy, as well as a second-line agent in the treatment of congestive heart failure (only in those intolerant of ACE inhibitors).
• Pharmacology: Angiotensin II, the principal pressor agent of the renin-angiotensin system, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme [kininase II]. It is responsible for effects such as vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Eprosartan selectively blocks the binding of angiotensin II to the AT₁ receptor, which in turn leads to multiple effects including vasodilation, a reduction in the secretion of vasopressin, and reduction in the production and secretion of aldosterone. The resulting effect is a decrease in blood pressure.
• Toxicity: There was no mortality in rats and mice receiving oral doses of up to 3000 mg eprosartan/kg and in dogs receiving oral doses of up to 1000 mg eprosartan/kg.
• Affected Organisms: Humans and other mammals
• Biotransformation: Eprosartan is not metabolized by the cytochrome P450 system. It is mainly eliminated as unchanged drug. Less than 2% of an oral dose is excreted in the urine as a glucuronide.
• Absorption: Absolute bioavailability following a single 300 mg oral dose of eprosartan is approximately 13%. Administering eprosartan with food delays absorption.
• Half Life: The terminal elimination half-life of eprosartan following oral administration is typically 5 to 9 hours.
• Protein Binding: Plasma protein binding of eprosartan is high (approximately 98%) and constant over the concentration range achieved with therapeutic doses.
• References: Ruilope L, Jager B, Prichard B: Eprosartan versus enalapril in elderly patients with hypertension: a double-blind, randomized trial. Blood Press. 2001;10(4):223-9. [Pubmed] ; Hedner T: The clinical profile of the angiotensin II receptor blocker eprosartan. J Hypertens Suppl. 2002 Jun;20(5):S33-8. [Pubmed] ; Puig JG, Lopez MA, Bueso TS, Bernardino JI, Jimenez RT: Clinical profile of eprosartan. Cardiovasc Drugs Ther. 2002 Dec;16(6):543-9. [Pubmed] ; Ruilope L, Jager B: Eprosartan for the treatment of hypertension. Expert Opin Pharmacother. 2003 Jan;4(1):107-14. [Pubmed] ; de la Sierra A, Ram CV: Introduction: The pharmacological profile of eprosartan--implications for cerebrovascular and cardiovascular risk reduction. Curr Med Res Opin. 2007 Nov;23 Suppl 5:S1-3. [Pubmed] ; Blankestijn PJ, Rupp H: Clinical profile of eprosartan: a different angiotensin II receptor blocker. Cardiovasc Hematol Agents Med Chem. 2008 Oct;6(4):253-7. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Toronto Research Chemicals - E590100

Eprosartan is a prototype of the imidazoleacrylic acid angiotensin II receptor antagonists. Eprosartan is an antihypertensive.

Toronto Research Chemicals - E590095

(Z)-Eprosartan is the Z-isomer of Eprosartan (E590100), as an impurity in tablets.

REFERENCES

• Ruilope L, Jager B, Prichard B: Eprosartan versus enalapril in elderly patients with hypertension: a double-blind, randomized trial. Blood Press. 2001;10(4):223-9. Pubmed
• Hedner T: The clinical profile of the angiotensin II receptor blocker eprosartan. J Hypertens Suppl. 2002 Jun;20(5):S33-8. Pubmed
• Puig JG, Lopez MA, Bueso TS, Bernardino JI, Jimenez RT: Clinical profile of eprosartan. Cardiovasc Drugs Ther. 2002 Dec;16(6):543-9. Pubmed
• Ruilope L, Jager B: Eprosartan for the treatment of hypertension. Expert Opin Pharmacother. 2003 Jan;4(1):107-14. Pubmed
• de la Sierra A, Ram CV: Introduction: The pharmacological profile of eprosartan--implications for cerebrovascular and cardiovascular risk reduction. Curr Med Res Opin. 2007 Nov;23 Suppl 5:S1-3. Pubmed
• Blankestijn PJ, Rupp H: Clinical profile of eprosartan: a different angiotensin II receptor blocker. Cardiovasc Hematol Agents Med Chem. 2008 Oct;6(4):253-7. Pubmed
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