2-(4-{[4-methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-1-yl]methyl}phenyl)benzoic acid

• ChemBase ID: 841
• Molecular Formular: C33H30N4O2
• Molecular Mass: 514.6169
• Monoisotopic Mass: 514.23687622
• SMILES: OC(=O)c1c(c2ccc(Cn3c4c(nc3CCC)c(cc(c4)c3n(c4c(n3)cccc4)C)C)cc2)cccc1
• Canonical SMILES: CCCc1nc2c(n1Cc1ccc(cc1)c1ccccc1C(=O)O)cc(cc2C)c1nc2c(n1C)cccc2
• InChI: InChI=1S/C33H30N4O2/c1-4-9-30-35-31-21(2)18-24(32-34-27-12-7-8-13-28(27)36(32)3)19-29(31)37(30)20-22-14-16-23(17-15-22)25-10-5-6-11-26(25)33(38)39/h5-8,10-19H,4,9,20H2,1-3H3,(H,38,39)
• InChIKey: RMMXLENWKUUMAY-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-(4-{[4-methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-1-yl]methyl}phenyl)benzoic acid
• IUPAC Traditional name: telmisartan; 2-(4-{[4-methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-1-yl]methyl}phenyl)benzoic acid
• Brand Name: Micardis; Micardis HCT; Pritor
• Synonyms: Micardis; Targit; Temax; BIBR277; 4'-((1,7'-Dimethyl-2'-propyl-1H,3'H-[2,5'-bibenzo[d]imidazol]-3'-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid; BIBR 277; BIBR 277SE; telmisartan; Telmisartan; 4′[(1,4′-Dimethyl-2′-propyl[2,6′-bi-1H-benzimidazol]-1′-yl)methyl][1,1′-biphenyl]-2-carboxylic acid; Telmisartan; Kinzal; Telma; Teleact D; 4’-[(1,4’-Dimethyl-2’-propyl[2,6’-bi-H-benzimidazol]-1’-yl)methyl][1,1’-biphenyl]-2-carboxylic Acid; 4'-[[4-Methyl-6-(1-methyl-2-benzimidazolyl)-2-propyl-1-benzimidazolyl]methyl]-2-biphenylcarboxylic Acid; Pritor

Database IDs

• CAS Number: 144701-48-4
• MDL Number: MFCD00918125
• PubChem SID: 46505370; 160964304
• PubChem CID: 65999

CALCULATED PROPERTIES

JChem

• Acid pKa: 3.645957
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): 6.091965
• LogD (pH = 7.4): 5.0242934
• Log P: 6.040852
• Molar Refractivity: 164.4888 cm^3
• Polarizability: 63.009975 Å^3
• Polar Surface Area: 72.94 Å^2
• Rotatable Bonds: 7
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 6.66
• LOG S: -5.17
• Solubility (Water): 3.50e-03 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO: >5 mg/mL at 60 °C; H2O: insoluble; Practically insoluble
• Apperance: white solid; White Solid
• Melting Point: 261-263°C
• Hydrophobicity(logP): 7.7

Safety Information

• Storage Condition: -20°C; Hygroscopic, -20°C Freezer, Under Inert Atmosphere
• Storage Warning: IRRITANT
• German water hazard class: 2
• TSCA Listed: false
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Pharmacology Properties

• Mechanism of Action: Angiotensin II (AT 1 ) receptor antagonist

Product Information

• Purity: ≥98% (HPLC); 95+%; 98%
• Salt Data: Free Base
• Application(s): Antihypertensive agent
• Empirical Formula (Hill Notation): C33H30N4O2

DETAILS

DrugBank - DB00966

• Drug Groups: approved; investigational
• Description: Telmisartan is an angiotensin II receptor antagonist (ARB) used in the management of hypertension. Generally, angiotensin II receptor blockers (ARBs) such as telmisartan bind to the angiotensin II type 1 (AT1) receptors with high affinity, causing inhibition of the action of angiotensin II on vascular smooth muscle, ultimately leading to a reduction in arterial blood pressure. Recent studies suggest that telmisartan may also have PPAR-gamma agonistic properties that could potentially confer beneficial metabolic effects.
• Indication: Used alone or in combination with other classes of antihypertensives for the treatment of hypertension. Also used in the treatment of diabetic nephropathy in hypertensive patients with type 2 diabetes mellitus, as well as the treatment of congestive heart failure (only in patients who cannot tolerate ACE inhibitors).
• Pharmacology: Telmisartan is an orally active nonpeptide angiotensin II antagonist that acts on the AT₁ receptor subtype. It has the highest affinity for the AT₁ receptor among commercially available ARBS and has minimal affinity for the AT₂ receptor. New studies suggest that telmisartan may also have PPARγ agonistic properties that could potentially confer beneficial metabolic effects, as PPARγ is a nuclear receptor that regulates specific gene transcription, and whose target genes are involved in the regulation of glucose and lipid metabolism, as well as anti-inflammatory responses. This observation is currently being explored in clinical trials. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan works by blocking the vasoconstrictor and aldosterone secretory effects of angiotensin II.
• Toxicity: Intravenous LD₅₀ in rats is 150-200 mg/kg in males and 200 to 250 mg/kg in females. Acute oral toxicity is low: no deaths and no changes occurred in rats or dogs at 2000 mg/kg, the highest dose tested. Limited data are available with regard to overdosage in humans. The most likely manifestations of overdosage with telmisartan would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation.
• Affected Organisms: Humans and other mammals
• Biotransformation: Minimally metabolized by conjugation to form a pharmacologically inactive acylglucuronide; the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.
• Absorption: Absolute bioavailability depends on dosage. Food slightly decreases the bioavailability (a decrease of about 6% is seen when the 40-mg dose is administered with food).
• Half Life: Bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours.
• Protein Binding: Highly bound to plasma proteins (>99.5%), mainly albumin and a1-acid glycoprotein. Binding is not dose-dependent.
• Elimination: Following either intravenous or oral administration of 14C-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively).
• Distribution: * 500 L
• Clearance: * >800 mL/min
• References: Sharpe M, Jarvis B, Goa KL: Telmisartan: a review of its use in hypertension. Drugs. 2001;61(10):1501-29. [Pubmed] ; Smith DH: Treatment of hypertension with an angiotensin II-receptor antagonist compared with an angiotensin-converting enzyme inhibitor: a review of clinical studies of telmisartan and enalapril. Clin Ther. 2002 Oct;24(10):1484-501. [Pubmed] ; Kumar AS, Ghosh S, Mehta GN: Efficient and improved synthesis of Telmisartan. Beilstein J Org Chem. 2010 Mar 11;6:25. [Pubmed] ; Galzerano D, Capogrosso C, Di Michele S, Galzerano A, Paparello P, Lama D, Gaudio C: New standards in hypertension and cardiovascular risk management: focus on telmisartan. Vasc Health Risk Manag. 2010 Mar 24;6:113-33. [Pubmed] ; Kumar AS, Ghosh S, Mehta GN: Efficient and improved synthesis of Telmisartan. Beilstein J Org Chem. 2010 Mar 11;6:25. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1738

Research Area: Cardiovascular Disease
Biological Activity:
Telmisartan o(Micardis) is an angiotensin II receptor antagonist (ARB) used in the management of hypertension. In addition to blocking the Renin-Angiotensin System (RAS), telmisartan acts as a selective modulator of Peroxisome proliferator-activated receptor gamma (PPAR-γ), a central regulator of insulin and glucose metabolism. Telmisartan has binding affinity 3000 times greater for AT1 than AT2 receptors. Telmisartan also has the longest half life (24 hrs) of all angiotensin II type 1 receptor antagonists. [1]

Sigma Aldrich - T8949

Biochem/physiol Actions
Telmisartan is a non-peptide AT1 angiotensin receptor antagonist.

Toronto Research Chemicals - T017000

Telmisartan is an angiotensin II receptor antagonist.

REFERENCES

• Sharpe M, Jarvis B, Goa KL: Telmisartan: a review of its use in hypertension. Drugs. 2001;61(10):1501-29. Pubmed
• Smith DH: Treatment of hypertension with an angiotensin II-receptor antagonist compared with an angiotensin-converting enzyme inhibitor: a review of clinical studies of telmisartan and enalapril. Clin Ther. 2002 Oct;24(10):1484-501. Pubmed
• Kumar AS, Ghosh S, Mehta GN: Efficient and improved synthesis of Telmisartan. Beilstein J Org Chem. 2010 Mar 11;6:25. Pubmed
• Galzerano D, Capogrosso C, Di Michele S, Galzerano A, Paparello P, Lama D, Gaudio C: New standards in hypertension and cardiovascular risk management: focus on telmisartan. Vasc Health Risk Manag. 2010 Mar 24;6:113-33. PubmedKumar AS, Ghosh S, Mehta GN: Efficient and improved synthesis of Telmisartan. Beilstein J Org Chem. 2010 Mar 11;6:25. Pubmed
• http://en.wikipedia.org/wiki/Telmisartan
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• Sharpe, M. et al., Drugs, 2001, 61, 1501-1529, (rev)