TELMISARTAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C33H30N4O2
Molecular Weight	514.6169
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCC1=NC2=C(C=C(C=C2C)C3=NC4=C(C=CC=C4)N3C)N1CC5=CC=C(C=C5)C6=CC=CC=C6C(O)=O

InChI

InChIKey=RMMXLENWKUUMAY-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00966
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf

Telmisartan is an orally active nonpeptide angiotensin II antagonist that acts on the AT1 receptor subtype. It was discovered by Boehringer Ingelheim and launched in 1999 as Micardis. 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. 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. Used alone or in combination with other classes of antihypertensives for the treatment of hypertension. Telmisartan is 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).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Arachidonic acid metabolism 6 Target ID: map00590 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26632190	Inhibitor 8504	49.5 µM [IC50]
Peroxisome proliferator-activated receptor gamma 118 Target ID: CHEMBL235 Sources: http://www.drugbank.ca/drugs/DB00966	Partial Agonist 297	12.2 µM [IC50]
Type-1 angiotensin II receptor 41 Target ID: CHEMBL227 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf	Antagonist 2849	3.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf	Primary		Approved 8583	MICARDIS Approved Use MICARDIS is an angiotensin II receptor blocker (ARB) indicated for: • Treatment of hypertension • Cardiovascular (CV) risk reduction in patients unable to take ACE inhibitors Launch Date 1998
Cardiovascular diseases 72 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf	Preventing		Approved 8583	MICARDIS Approved Use MICARDIS is an angiotensin II receptor blocker (ARB) indicated for: • Treatment of hypertension • Cardiovascular (CV) risk reduction in patients unable to take ACE inhibitors Launch Date 1998

C_max

Value	Dose	Co-administered	Analyte	Population
3200 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11014323	160 mg single, intravenous dose: 160 mg route of administration: Intravenous experiment type: SINGLE co-administered:		TELMISARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
3320 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11014323	160 mg single, intravenous dose: 160 mg route of administration: Intravenous experiment type: SINGLE co-administered:		TELMISARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
17.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11014323	160 mg single, intravenous dose: 160 mg route of administration: Intravenous experiment type: SINGLE co-administered:		TELMISARTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
160 mg single, intravenous Highest studied dose Dose: 160 mg Route: intravenous Route: single Dose: 160 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11014323	healthy, 18 – 50 Health Status: healthy Age Group: 18 – 50 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/11014323	Sources: https://pubmed.ncbi.nlm.nih.gov/11014323
320 mg 1 times / day multiple, oral Highest studied dose Dose: 320 mg, 1 times / day Route: oral Route: multiple Dose: 320 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11014323	healthy, 18 – 50 Health Status: healthy Age Group: 18 – 50 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/11014323	Sources: https://pubmed.ncbi.nlm.nih.gov/11014323
80 mg 1 times / day multiple, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf	Disc. AE: Disorder fetal, Hypotension... AEs leading to discontinuation/dose reduction: Disorder fetal Hypotension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf

AEs

AE	Significance	Dose	Population
Disorder fetal	Disc. AE	80 mg 1 times / day multiple, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf
Hypotension	Disc. AE	80 mg 1 times / day multiple, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2J2 33 CYP2C8 1057 CYP2B6 926 CYP2C19 2057 BSEP 550 CYP1A2 2153 MRP2 499 Kv1.5 27 MRP4 290 BCRP 910 P-gp 1741 MRP3 246	UGT1A1 479 UGT2B7 456 UGT1A3 470 UGT1A9 423 CYP 303 OATP1B1 503 UGT2B15 236 UGT1A4 399 OATP1B3 435	rCYP 6

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20850_MICARDIS_biopharmr_P1.pdf#page=11 \| https://pubmed.ncbi.nlm.nih.gov/23033255/ Page: 11.0	minor [IC50 4.78 uM]
MRP4 345	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	moderate [IC50 36 uM]
MRP3 326	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	moderate [IC50 60 uM]
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20850_MICARDIS_biopharmr_P1.pdf#page=11 \| https://pubmed.ncbi.nlm.nih.gov/23033255/ Page: 11.0	no [IC50 >50 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20850_MICARDIS_biopharmr_P1.pdf#page=11 \| https://pubmed.ncbi.nlm.nih.gov/23033255/ Page: 11.0	no [IC50 >50 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20850_MICARDIS_biopharmr_P1.pdf#page=11 \| https://pubmed.ncbi.nlm.nih.gov/23033255/ Page: 11.0	no [IC50 >50 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20850_MICARDIS_biopharmr_P1.pdf#page=11 Page: 11.0	no
rCYP 6	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20850_MICARDIS_pharmr_P2.pdf#page=3 Page: 3.0	no
CYP2J2 36	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23033255/	yes [IC50 0.42 uM]
BSEP 554	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25426072/ \| https://pubmed.ncbi.nlm.nih.gov/23956101/	yes [IC50 16.2 uM]
Kv1.5 42	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18664324/	yes [IC50 2.25 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28867723/	yes [IC50 49.5 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020850s040lbl.pdf#page=7 \| https://pubmed.ncbi.nlm.nih.gov/23033255/ Page: 7.0	yes [IC50 >50 uM]
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24032744/	yes [Ki 14.3 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/26171231/	yes

Drug as victim

Target	Modality	Activity
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32294459/	likely
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32294459/	likely
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32294459/	likely
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32294459/	likely
UGT1A3 470	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20850_MICARDIS_biopharmr_P1.pdf#page=10 \| https://pubmed.ncbi.nlm.nih.gov/32294459/ Page: 10.0	major
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32294459/	minor
CYP 303	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20850_MICARDIS_biopharmr_P1.pdf#page=3 Page: 3.0	no
OATP1B1 503	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16611857/	no
OATP1B3 435	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16611857/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/18664324/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9434	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9434
ChemicalBook	CB4266172	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4266172
eMolecules	2725948	https://www.emolecules.com/cgi-bin/more?vid=2725948
MolPort	MolPort-003-666-621	https://www.molport.com/shop/molecule-link/MolPort-003-666-621
Selleck Chemicals	Telmisartan(Micardis)	http://www.selleckchem.com/products/Telmisartan(Micardis).html
ZINC	ZINC000001530886	http://zinc15.docking.org/substances/ZINC000001530886

PubMed

Title	Date	PubMed
Experimental design approach for the optimisation of a HPLC-fluorimetric method for the quantitation of the angiotensin II receptor antagonist telmisartan in urine.	2003-08-08	12899971
Telmisartan vs losartan plus hydrochlorothiazide in the treatment of mild-to-moderate essential hypertension--a randomised ABPM study.	2003-08	12874615
Prospective, randomized, open-label, blinded-endpoint (PROBE) designed trials yield the same results as double-blind, placebo-controlled trials with respect to ABPM measurements.	2003-07	12817175
Cardiology patient page. Angiotensin receptor blockers.	2003-06-24	12821593
Effect of telmisartan on the proteinuria and circadian blood pressure profile in chronic renal patients.	2003-06-24	12818479
[Improved protection of heart and kidneys in the hypertensive patient. ACE inhibitor and AT1 blocker combined?].	2003-06-05	12854231
Comparison of telmisartan versus losartan: meta-analysis of titration-to-response studies.	2003-06	12900588
Defining the antihypertensive properties of the angiotensin receptor blocker telmisartan by a practice-based clinical trial.	2003-06	12799094
Different effect of antihypertensive drugs on conduit artery endothelial function.	2003-06	12719441
The ongoing telmisartan alone and in combination with ramipril global endpoint trial program.	2003-05-22	12781906
How cost-effective are new preventive strategies for cardiovascular disease?	2003-05-22	12781905
[Morning or evening, in the physicians office or at home. Measured blood pressure values have their peculiarities].	2003-05-15	12822237
Neonatal acute renal failure secondary to maternal exposure to telmisartan, angiotensin II receptor antagonist.	2003-05-07	12732865
[Effects of angiotensin receptor inhibitors on cardiovascular endpoints--current and future evidence].	2003-05-04	12785235
[Diurnal blood pressure control in the optimal treatment of hypertension].	2003-05-04	12785233
[Therapy of hypertension. Pulse pressure must also be reduced].	2003-05-01	12808823
Efficacy and tolerability of fixed-dose combinations of telmisartan plus HCTZ compared with losartan plus HCTZ in patients with essential hypertension.	2003-05	12800457
Angioedema induced by angiotensin II blocker telmisartan.	2003-05	12752339
Search of antimicrobial activity of selected non-antibiotic drugs.	2003-04-03	12669766
Simultaneous determination of hydrochlorothiazide and several angiotensin-II-receptor antagonists by capillary electrophoresis.	2003-02-26	12609672
Angiotensin-converting enzyme inhibitors for stroke prevention: is there HOPE for PROGRESS After LIFE?	2003-02	12574534
Evaluation of angiotensin II receptor blockers for 24-hour blood pressure control: meta-analysis of a clinical database.	2003-01-31	12556655
[Despite therapy morning dangerous RR spikes. Headache and vertigo are alarm signals].	2003-01-23	12619236
ABPM comparison of the anti-hypertensive profiles of telmisartan and enalapril in patients with mild-to-moderate essential hypertension.	2003-01-16	12526280
Optimization and validation of a micellar electrokinetic chromatographic method for the analysis of several angiotensin-II-receptor antagonists.	2003-01-10	12564683
Angiotensin II receptor blockade: is there truly a benefit of adding an ACE inhibitor?	2003-01	12511526
Drug interactions with angiotensin receptor blockers: a comparison with other antihypertensives.	2003	12862505
Effects of telmisartan and losartan on left ventricular mass in mild-to-moderate hypertension. A randomized, double-blind trial.	2003	12824726
Optimization and validation of a capillary zone electrophoretic method for the analysis of several angiotensin-II-receptor antagonists.	2002-12-06	12498264
Gateways to clinical trials.	2002-12	12616965
Comparison of trough effect of telmisartan vs perindopril using self blood pressure measurement: EVERESTE study.	2002-12	12522468
[Lowering blood pressure with sartans. Are there differences?].	2002-11-21	12532530
[These hypertensive patients are especially at risk for myocardial infarct in the morning. Screen for non-dippers].	2002-11-14	12534089
Angiotensin blockade prevents type 2 diabetes by formation of fat cells.	2002-11	12411451
Amlodipine versus Angiotensin-receptor blockers for nonhypertension indications.	2002-11	12398574
[Evaluation of blood pressure self-monitoring of the residual efficacy of telmisartan compared to perindopril. The EVERESTE study].	2002-10-09	12365090
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.	2002-10	12462282
A multicenter, open-label study of the efficacy and safety of telmisartan in mild to moderate hypertensive patients.	2002-10	12426643
[Tendency and prospect of the development of new ARBs].	2002-10	12397678
A new fixed-dose combination for added blood pressure control: telmisartan plus hydrochlorothiazide.	2002-09-19	12235918
Effects of telmisartan on arterial stiffness in Type 2 diabetes patients with essential hypertension.	2002-09	12563568
Stimulation of collagen gel contraction by angiotensin II and III in cardiac fibroblasts.	2002-09	12563566
The efficacy and tolerability of an angiotensin II receptor blocker, telmisartan, in Thai patients with mild to moderate essential hypertension.	2002-09	12450074
Sympatholytic properties of several AT1-receptor antagonists in the isolated rabbit thoracic aorta.	2002-09	12195125
In vitro and in vivo characterization of the activity of telmisartan: an insurmountable angiotensin II receptor antagonist.	2002-09	12183667
Sympatho-inhibitory properties of various AT1 receptor antagonists.	2002-06	12184061
[Angiotensin II receptor blocker telmisartan: effect on 24-hour blood pressure profile and left ventricular hypertrophy in patients with hypertension].	2002	12494207
[Hypotensive effects of telmisartan on blood pressure during rest and exercise in patients with mild and moderate arterial hypertension].	2002	12474774
Long-term efficacy and tolerability of telmisartan as monotherapy and in combination with other antihypertensive medications.	2002	12458653
Telmisartan. BIBR 277, Micardis, Pritor.	2002	12455201

Patents

Sample Use Guides

In Vivo Use Guide

Hypertension - 40 to 80 mg once daily Cardiovascular Risk Reduction - 80 mg once daily

Route of Administration: Oral

In Vitro Use Guide

Telmisartan (0.01-10 nmol/l) concentration dependently attenuated the angiotensin II-mediated (1 nmol/l) enhancement of EFS-evoked sympathetic outflow in the isolated rabbit thoracic aorta.

Name

Type

Language

TELMISARTAN

Official Name

English

KINZALKOMB COMPONENT TELMISARTAN

Preferred Name

English

BIBR 277 SE

Code

English

TELMISARTAN [EMA EPAR]

Common Name

English

KINZALMONO

Brand Name

English

TELMISARTAN [EP IMPURITY]

Common Name

English

BIBR-277

Code

English

TELMISARTAN [GREEN BOOK]

Common Name

English

TELMISARTAN [USP MONOGRAPH]

Common Name

English

TELMISARTAN [USP-RS]

Common Name

English

TELMISARTAN [MART.]

Common Name

English

TOLURA

Brand Name

English

TELMISARTAN [JAN]

Common Name

English

TELMISARTAN TEVA

Brand Name

English

TELMISARTAN [EMA EPAR VETERINARY]

Common Name

English

MICARDISPLUS COMPONENT TELMISARTAN

Brand Name

English

BIBR-277 SE

Code

English

PRITORPLUS COMPONENT TELMISARTAN

Brand Name

English

(1,1'-BIPHENYL)-2-CARBOXYLIC ACID, 4'-((1,4'-DIMETHYL-2'-PROPYL(2,6'-BI-1H-BENZIMIDAZOL)-1'-YL)METHYL)-

Common Name

English

TELMISARTAN [USAN]

Common Name

English

TWYNSTA COMPONENT TELMISARTAN

Common Name

English

ONDUARP COMPONENT TELMISARTAN

Brand Name

English

telmisartan [INN]

Common Name

English

MICARDIS HCT COMPONENT TELMISARTAN

Common Name

English

C09CA07

Code

English

TELMISARTAN [EP MONOGRAPH]

Common Name

English

PRITOR

Brand Name

English

TELMISARTAN [MI]

Common Name

English

Telmisartan [WHO-DD]

Common Name

English

MICARDIS

Brand Name

English

TELMISARTAN [VANDF]

Common Name

English

BIBR-277-SE

Code

English

TELMISARTAN TEVA PHARMA

Brand Name

English

SEMINTRA

Brand Name

English

TELMISARTAN [ORANGE BOOK]

Common Name

English

TELMISARTAN [HSDB]

Common Name

English

TOLUCOMBI COMPONENT TELMISARTAN

Brand Name

English

TELMISARTAN ACTAVIS

Brand Name

English

4'-((4-METHYL-6-(1-METHYL-2-BENZIMIDAZOLYL)-2-PROPYL-1-BENZIMIDAZOLYL)METHYL)-2-BIPHENYLCARBOXYLIC ACID

Systematic Name

English

Classification Tree Code System Code

LIVERTOX

NBK548042