TELMISARTAN METHYL ESTER

Details

Stereochemistry	ACHIRAL
Molecular Formula	C34H32N4O2
Molecular Weight	528.6435
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(C=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C(=O)OC)C5=NC6=C(C=CC=C6)N5C

InChI

InChIKey=HJCCZIABCSDUPE-UHFFFAOYSA-N

InChI=1S/C34H32N4O2/c1-5-10-31-36-32-22(2)19-25(33-35-28-13-8-9-14-29(28)37(33)3)20-30(32)38(31)21-23-15-17-24(18-16-23)26-11-6-7-12-27(26)34(39)40-4/h6-9,11-20H,5,10,21H2,1-4H3

HIDE SMILES / InChI

Molecular Formula	C34H32N4O2
Molecular Weight	528.6435
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 5 Target ID: map00590 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26632190	Inhibitor 8297	49.5 µM [IC50]
Peroxisome proliferator-activated receptor gamma 111 Target ID: CHEMBL235 Sources: http://www.drugbank.ca/drugs/DB00966	Partial Agonist 290	12.2 µM [IC50]
Type-1 angiotensin II receptor 40 Target ID: CHEMBL227 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf	Antagonist 2778	3.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf	Primary		Approved 8429	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 71 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf	Preventing		Approved 8429	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 Page: p.159	healthy, 18 – 50 n = 12 Health Status: healthy Age Group: 18 – 50 Sex: M Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/11014323 Page: p.159	Sources: https://pubmed.ncbi.nlm.nih.gov/11014323 Page: p.159
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 Page: p.161	healthy, 18 – 50 n = 10 Health Status: healthy Age Group: 18 – 50 Sex: M Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/11014323 Page: p.161	Sources: https://pubmed.ncbi.nlm.nih.gov/11014323 Page: p.161
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 Page: p.1	unhealthy Health Status: unhealthy Condition: Hypertension\|Cardiovascular Risk Reduction Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf Page: p.1	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 Page: p.1

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 Page: p.1	unhealthy Health Status: unhealthy Condition: Hypertension\|Cardiovascular Risk Reduction Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf Page: p.1
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 Page: p.1	unhealthy Health Status: unhealthy Condition: Hypertension\|Cardiovascular Risk Reduction Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020850s032lbl.pdf Page: p.1

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
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
eMolecules	2725948	https://www.emolecules.com/cgi-bin/more?vid=2725948

PubMed

Title	Date	PubMed
[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
Gateways to clinical trials.	2002 Dec	12616965
Comparison of trough effect of telmisartan vs perindopril using self blood pressure measurement: EVERESTE study.	2002 Dec	12522468
Optimization and validation of a capillary zone electrophoretic method for the analysis of several angiotensin-II-receptor antagonists.	2002 Dec 6	12498264
[Evaluation of blood pressure self-monitoring of the residual efficacy of telmisartan compared to perindopril. The EVERESTE study].	2002 Jul-Aug	12365090
A new fixed-dose combination for added blood pressure control: telmisartan plus hydrochlorothiazide.	2002 Jul-Aug	12235918
Sympatho-inhibitory properties of various AT1 receptor antagonists.	2002 Jun	12184061
Angiotensin blockade prevents type 2 diabetes by formation of fat cells.	2002 Nov	12411451
Amlodipine versus Angiotensin-receptor blockers for nonhypertension indications.	2002 Nov	12398574
[These hypertensive patients are especially at risk for myocardial infarct in the morning. Screen for non-dippers].	2002 Nov 14	12534089
[Lowering blood pressure with sartans. Are there differences?].	2002 Nov 21	12532530
Search of antimicrobial activity of selected non-antibiotic drugs.	2002 Nov-Dec	12669766
ABPM comparison of the anti-hypertensive profiles of telmisartan and enalapril in patients with mild-to-moderate essential hypertension.	2002 Nov-Dec	12526280
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 Oct	12462282
A multicenter, open-label study of the efficacy and safety of telmisartan in mild to moderate hypertensive patients.	2002 Oct	12426643
[Tendency and prospect of the development of new ARBs].	2002 Oct	12397678
Effects of telmisartan on arterial stiffness in Type 2 diabetes patients with essential hypertension.	2002 Sep	12563568
Stimulation of collagen gel contraction by angiotensin II and III in cardiac fibroblasts.	2002 Sep	12563566
The efficacy and tolerability of an angiotensin II receptor blocker, telmisartan, in Thai patients with mild to moderate essential hypertension.	2002 Sep	12450074
Sympatholytic properties of several AT1-receptor antagonists in the isolated rabbit thoracic aorta.	2002 Sep	12195125
In vitro and in vivo characterization of the activity of telmisartan: an insurmountable angiotensin II receptor antagonist.	2002 Sep	12183667
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
Neonatal acute renal failure secondary to maternal exposure to telmisartan, angiotensin II receptor antagonist.	2003 Apr-May	12732865
Telmisartan vs losartan plus hydrochlorothiazide in the treatment of mild-to-moderate essential hypertension--a randomised ABPM study.	2003 Aug	12874615
Experimental design approach for the optimisation of a HPLC-fluorimetric method for the quantitation of the angiotensin II receptor antagonist telmisartan in urine.	2003 Aug 8	12899971
Angiotensin-converting enzyme inhibitors for stroke prevention: is there HOPE for PROGRESS After LIFE?	2003 Feb	12574534
Simultaneous determination of hydrochlorothiazide and several angiotensin-II-receptor antagonists by capillary electrophoresis.	2003 Feb 26	12609672
Angiotensin II receptor blockade: is there truly a benefit of adding an ACE inhibitor?	2003 Jan	12511526
Optimization and validation of a micellar electrokinetic chromatographic method for the analysis of several angiotensin-II-receptor antagonists.	2003 Jan 10	12564683
[Despite therapy morning dangerous RR spikes. Headache and vertigo are alarm signals].	2003 Jan 23	12619236
Evaluation of angiotensin II receptor blockers for 24-hour blood pressure control: meta-analysis of a clinical database.	2003 Jan-Feb	12556655
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 Jul	12817175
Comparison of telmisartan versus losartan: meta-analysis of titration-to-response studies.	2003 Jun	12900588
Defining the antihypertensive properties of the angiotensin receptor blocker telmisartan by a practice-based clinical trial.	2003 Jun	12799094
Different effect of antihypertensive drugs on conduit artery endothelial function.	2003 Jun	12719441
Cardiology patient page. Angiotensin receptor blockers.	2003 Jun 24	12821593
[Improved protection of heart and kidneys in the hypertensive patient. ACE inhibitor and AT1 blocker combined?].	2003 Jun 5	12854231
Efficacy and tolerability of fixed-dose combinations of telmisartan plus HCTZ compared with losartan plus HCTZ in patients with essential hypertension.	2003 May	12800457
Angioedema induced by angiotensin II blocker telmisartan.	2003 May	12752339
[Therapy of hypertension. Pulse pressure must also be reduced].	2003 May 1	12808823
[Morning or evening, in the physicians office or at home. Measured blood pressure values have their peculiarities].	2003 May 15	12822237
The ongoing telmisartan alone and in combination with ramipril global endpoint trial program.	2003 May 22	12781906
How cost-effective are new preventive strategies for cardiovascular disease?	2003 May 22	12781905
[Effects of angiotensin receptor inhibitors on cardiovascular endpoints--current and future evidence].	2003 May 4	12785235
[Diurnal blood pressure control in the optimal treatment of hypertension].	2003 May 4	12785233
Effect of telmisartan on the proteinuria and circadian blood pressure profile in chronic renal patients.	2003 May-Jun	12818479

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:59:05 GMT 2023` Edited by `admin` on `Fri Dec 15 15:59:05 GMT 2023`
Record UNII	9D4V6KU3AI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TELMISARTAN METHYL ESTER

Common Name

English

J3.264.806A

Code

English

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

Common Name

English

TEMISARTAN IMPURITY I [EP IMPURITY]

Common Name

English

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

Systematic Name

English

METHYL 4'-((2-PROPYL-4-METHYL-6-(1-METHYLBENZIMIDAZOL-2-YL)BENZIMIDAZOL-1-YL)METHYL)BIPHENYL-2-CARBOXYLATE

Systematic Name

English

METHYL 4-((1,7-DIMETHYL-2-PROPYL-1H,3H-(2,5-BIBENZIMIDAZOL)-3-YL)METHYL)(1,1-BIPHENYL)-2-CARBOXYLATE

Systematic Name

English

Code System Code Type Description

CAS

528560-93-2