Banner
Identification
Name Telmisartan
Accession Number DB00966 (APRD01247)
Type small molecule
Groups approved
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.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • BIBR 277
  • BIBR 277SE
  • telmisartan
Brand names
  • Micardis
  • Micardis HCT
  • Pritor
Brand name mixtures
  • Micardis Plus (Hydrochlorothiazide + Telmisartan)
Categories
  • Angiotensin-converting Enzyme Inhibitors
  • Angiotensin II Type 1 Receptor Blockers
CAS number 144701-48-4
Weight Average: 514.6169
Monoisotopic: 514.236876224
Chemical Formula C33H30N4O2
InChI Key InChIKey=RMMXLENWKUUMAY-UHFFFAOYSA-N
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)
Plain Text
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
SMILES
CCCC1=NC2=C(C=C(C=C2C)C2=NC3=C(C=CC=C3)N2C)N1CC1=CC=C(C=C1)C1=C(C=CC=C1)C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Biphenyl and Derivatives
  • Cinnamates
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Benzoates
  • Benzimidazoles
  • Carboxylic Acids and Derivatives
  • Phenylpropenes
  • Benzene and Derivatives
  • Biphenyl and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Cinnamaldehydes
  • Imines
  • Benzoyl Derivatives
  • Cyanamides
  • Cinnamates
Pharmacology
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).
Pharmacodynamics 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.
Mechanism of action Telmisartan interferes with the binding of angiotensin II to the angiotensin II AT1-receptor by binding reversibly and selectively to the receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. Telmisartan does not inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels. Studies also suggest that telmisartan is a partial agonist of PPARγ, which is an established target for antidiabetic drugs. This suggests that telmisartan can improve carbohydrate and lipid metabolism, as well as control insulin resistance without causing the side effects that are associated with full PPARγ activators.
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).
Volume of distribution
  • 500 L
Protein binding Highly bound to plasma proteins (>99.5%), mainly albumin and a1-acid glycoprotein. Binding is not dose-dependent.
Metabolism

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.
Route of 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).
Half life Bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours.
Clearance
  • >800 mL/min
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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Boehringer ingelheim
Packagers
Dosage forms
Form Route Strength
Tablet Oral 20 mg
Tablet Oral 40 mg
Tablet Oral 80 mg
Prices
Unit description Cost Unit
Micardis 30 40 mg tablet Box 110.11 USD box
Micardis HCT 30 40-12.5 mg tablet Box 106.34 USD box
Micardis HCT 30 80-12.5 mg tablet Box 106.18 USD box
Micardis 30 80 mg tablet Box 103.92 USD box
Micardis HCT 30 80-25 mg tablet Box 100.48 USD box
Micardis 30 20 mg tablet Box 99.7 USD box
Micardis 20 mg tablet 3.29 USD tablet
Micardis hct 40-12.5 mg tablet 3.29 USD tablet
Micardis hct 80-12.5 mg tablet 3.29 USD tablet
Micardis hct 80-25 mg tablet 3.29 USD tablet
Micardis 40 mg tablet 2.24 USD tablet
Micardis 80 mg tablet 2.24 USD tablet
Patents
Country Patent Number Approved Expires
United States 6358986 2000-01-10 2020-01-10
United States 5591762 1994-01-07 2014-01-07
Canada 2060624 1999-12-21 2012-02-04
Properties
State solid
Melting point 261-263oC
Experimental Properties
Property Value Source
water solubility Practically insoluble PhysProp
logP 7.7 PhysProp
Caco2 permeability -4.82 [ADME Research, USCD] BiGG
Predicted Properties
Property Value Source
water solubility 3.50e-03 g/l ALOGPS
logP 6.66 ALOGPS
logP 5.14 ChemAxon Molconvert
logS -5.17 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 72.94 ChemAxon Molconvert
rotatable bond count 7 ChemAxon Molconvert
refractivity 164.49 ChemAxon Molconvert
polarizability 58.61 ChemAxon Molconvert
References
Synthesis Reference
  1. Kumar AS, Ghosh S, Mehta GN: Efficient and improved synthesis of Telmisartan. Beilstein J Org Chem. 2010 Mar 11;6:25. Pubmed
General Reference
  1. Sharpe M, Jarvis B, Goa KL: Telmisartan: a review of its use in hypertension. Drugs. 2001;61(10):1501-29. Pubmed
  2. 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
  3. Kumar AS, Ghosh S, Mehta GN: Efficient and improved synthesis of Telmisartan. Beilstein J Org Chem. 2010 Mar 11;6:25. Pubmed
  4. 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
External Links
Resource Link
KEGG Drug D00627 Link_out
KEGG Compound C07710 Link_out
PubChem Compound 65999 Link_out
PubChem Substance 46505370 Link_out
ChemSpider 59391 Link_out
ChEBI 9434 Link_out
ChEMBL 9434 Link_out
Therapeutic Targets Database DAP000766 Link_out
PharmGKB PA451605 Link_out
Drug Product Database 2240770 Link_out
RxList http://www.rxlist.com/cgi/generic2/telmisartan.htm Link_out
Drugs.com http://www.drugs.com/cdi/telmisartan.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/mic1592.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Telmisartan Link_out
ATC Codes
  • C09CA07
AHFS Codes
  • 24:32.08
PDB Entries Not Available
FDA label show (47.4 KB)
MSDS show (101 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Type-1 angiotensin II receptor

Pharmacological action: yes
Actions: antagonist

Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

Organism class: human
UniProt ID: P30556 Link_out
Gene: AGTR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Karlberg BE, Lins LE, Hermansson K: Efficacy and safety of telmisartan, a selective AT1 receptor antagonist, compared with enalapril in elderly patients with primary hypertension. TEES Study Group. J Hypertens. 1999 Feb;17(2):293-302. Pubmed
  3. Balt JC, Mathy MJ, Nap A, Pfaffendorf M, van Zwieten PA: Effect of the AT1-receptor antagonists losartan, irbesartan, and telmisartan on angiotensin II-induced facilitation of sympathetic neurotransmission in the rat mesenteric artery. J Cardiovasc Pharmacol. 2001 Jul;38(1):141-8. Pubmed
  4. Gohlke P, Weiss S, Jansen A, Wienen W, Stangier J, Rascher W, Culman J, Unger T: AT1 receptor antagonist telmisartan administered peripherally inhibits central responses to angiotensin II in conscious rats. J Pharmacol Exp Ther. 2001 Jul;298(1):62-70. Pubmed
  5. Strohmenger HU, Lindner KH, Wienen W, Vogt J: Effects of the AT1-selective angiotensin II antagonist, telmisartan, on hemodynamics and ventricular function after cardiopulmonary resuscitation in pigs. Resuscitation. 1997 Aug;35(1):61-8. Pubmed
  6. Fujimoto M, Masuzaki H, Tanaka T, Yasue S, Tomita T, Okazawa K, Fujikura J, Chusho H, Ebihara K, Hayashi T, Hosoda K, Nakao K: An angiotensin II AT1 receptor antagonist, telmisartan augments glucose uptake and GLUT4 protein expression in 3T3-L1 adipocytes. FEBS Lett. 2004 Oct 22;576(3):492-7. Pubmed
  7. Sharpe M, Jarvis B, Goa KL: Telmisartan: a review of its use in hypertension. Drugs. 2001;61(10):1501-29. Pubmed
  8. McClellan KJ, Markham A: Telmisartan. Drugs. 1998 Dec;56(6):1039-44; discussion 1045-6. Pubmed
  9. 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# Tagami T, Yamamoto H, Moriyama K, Sawai K, Usui T, Shimatsu A, Naruse M: A selective peroxisome proliferator-activated receptor-gamma modulator, telmisartan, binds to the receptor in a different fashion from thiazolidinediones. Endocrinology. 2009 Feb;150(2):862-70. Epub 2009 Jan 15. Pubmed
  10. Imayama I, Ichiki T, Inanaga K, Ohtsubo H, Fukuyama K, Ono H, Hashiguchi Y, Sunagawa K: Telmisartan downregulates angiotensin II type 1 receptor through activation of peroxisome proliferator-activated receptor gamma. Cardiovasc Res. 2006 Oct 1;72(1):184-90. Epub 2006 Jul 21. Pubmed
  11. Kurtz TW: Beyond the classic angiotensin-receptor-blocker profile. Nat Clin Pract Cardiovasc Med. 2008 Jul;5 Suppl 1:S19-26. Pubmed
  12. Yamagishi S, Takeuchi M: Telmisartan is a promising cardiometabolic sartan due to its unique PPAR-gamma-inducing property. Med Hypotheses. 2005;64(3):476-8. Pubmed
  13. Yamagishi S, Nakamura K, Matsui T: Potential utility of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-modulating activity for the treatment of cardiometabolic disorders. Curr Mol Med. 2007 Aug;7(5):463-9. Pubmed

2. Peroxisome proliferator-activated receptor gamma

Pharmacological action: yes
Actions: partial agonist

Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis

Organism class: human
UniProt ID: P37231 Link_out
Gene: PPARG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tagami T, Yamamoto H, Moriyama K, Sawai K, Usui T, Shimatsu A, Naruse M: A selective peroxisome proliferator-activated receptor-gamma modulator, telmisartan, binds to the receptor in a different fashion from thiazolidinediones. Endocrinology. 2009 Feb;150(2):862-70. Epub 2009 Jan 15. Pubmed
  2. Imayama I, Ichiki T, Inanaga K, Ohtsubo H, Fukuyama K, Ono H, Hashiguchi Y, Sunagawa K: Telmisartan downregulates angiotensin II type 1 receptor through activation of peroxisome proliferator-activated receptor gamma. Cardiovasc Res. 2006 Oct 1;72(1):184-90. Epub 2006 Jul 21. Pubmed
  3. Kurtz TW: Beyond the classic angiotensin-receptor-blocker profile. Nat Clin Pract Cardiovasc Med. 2008 Jul;5 Suppl 1:S19-26. Pubmed
  4. Yamagishi S, Takeuchi M: Telmisartan is a promising cardiometabolic sartan due to its unique PPAR-gamma-inducing property. Med Hypotheses. 2005;64(3):476-8. Pubmed
  5. Kurtz TW: Treating the metabolic syndrome: telmisartan as a peroxisome proliferator-activated receptor-gamma activator. Acta Diabetol. 2005 Apr;42 Suppl 1:S9-16. Pubmed
  6. Yamagishi S, Nakamura K, Matsui T: Potential utility of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-modulating activity for the treatment of cardiometabolic disorders. Curr Mol Med. 2007 Aug;7(5):463-9. Pubmed
  7. Yamagishi S, Takenaka K, Inoue H: Role of insulin-sensitizing property of telmisartan, a commercially available angiotensin II type 1 receptor blocker in preventing the development of atrial fibrillation. Med Hypotheses. 2006;66(1):118-20. Epub 2005 Sep 12. Pubmed
Enzymes

1. Cytochrome P450 2C19

Actions: inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Weiss J, Sauer A, Divac N, Herzog M, Schwedhelm E, Boger RH, Haefeli WE, Benndorf RA: Interaction of angiotensin receptor type 1 blockers with ATP-binding cassette transporters. Biopharm Drug Dispos. 2010 Mar;31(2-3):150-61. Pubmed

2. Canalicular multispecific organic anion transporter 1

Actions: inhibitor

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Weiss J, Sauer A, Divac N, Herzog M, Schwedhelm E, Boger RH, Haefeli WE, Benndorf RA: Interaction of angiotensin receptor type 1 blockers with ATP-binding cassette transporters. Biopharm Drug Dispos. 2010 Mar;31(2-3):150-61. Pubmed

3. ATP-binding cassette sub-family G member 2

Actions: inhibitor

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Weiss J, Sauer A, Divac N, Herzog M, Schwedhelm E, Boger RH, Haefeli WE, Benndorf RA: Interaction of angiotensin receptor type 1 blockers with ATP-binding cassette transporters. Biopharm Drug Dispos. 2010 Mar;31(2-3):150-61. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:07

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.