AZILSARTAN MEDOXOMIL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C30H24N4O8
Molecular Weight	568.5336
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CCOC1=NC2=C(N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NOC(=O)N5)C(=CC=C2)C(=O)OCC6=C(C)OC(=O)O6

InChI

InChIKey=QJFSABGVXDWMIW-UHFFFAOYSA-N

InChI=1S/C30H24N4O8/c1-3-38-28-31-23-10-6-9-22(27(35)39-16-24-17(2)40-30(37)41-24)25(23)34(28)15-18-11-13-19(14-12-18)20-7-4-5-8-21(20)26-32-29(36)42-33-26/h4-14H,3,15-16H2,1-2H3,(H,32,33,36)

HIDE SMILES / InChI

Molecular Formula	C30H24N4O8
Molecular Weight	568.5336
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

TAK-536 (generic name: azilsartan) is an angiotensin II type 1 receptor blocker, discovered by Takeda and its mechanism of action is to lower blood pressure by inhibiting action of a vasopressor hormone Angiotensin II. Angiotensin II type 1 receptor antagonists have become an important drug class in the treatment of hypertension and heart failure. TAK-536 is in phase III clinical trial for treatment hypertension. This drug also known as active metabolite of the prodrug azilsartan medoxomil (also known as azilsartan kamedoxomil), but in some countries azilsartan rather than its prodrug is used for oral treatment.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Type-1 angiotensin II receptor 40	Antagonist 2,778		0.62 nM [IC50]
Type-1 angiotensin II receptor 40	Antagonist 2,778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567	Primary		Approved 8,429	EDARBI
Hypertension 567	Primary		Phase III 656	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
831.3 ng/mL	10 mg single, oral		AZILSARTAN plasma	Homo sapiens
141.3 ng/mL	10 mg single, oral		AZILSARTAN METABOLITE M-I plasma	Homo sapiens
179.3 ng/mL	10 mg single, oral		AZILSARTAN METABOLITE M-II plasma	Homo sapiens
888.3 ng/mL	5 mg single, oral		AZILSARTAN plasma	Homo sapiens
191.3 ng/mL	5 mg single, oral		AZILSARTAN METABOLITE M-I plasma	Homo sapiens
227.7 ng/mL	5 mg single, oral		AZILSARTAN METABOLITE M-II plasma	Homo sapiens
5355.71 ng/mL	80 mg single, oral	Chlorthalidone	AZILSARTAN plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
6871.7 ng*h/mL	10 mg single, oral		AZILSARTAN plasma	Homo sapiens
1420.5 ng*h/mL	10 mg single, oral		AZILSARTAN METABOLITE M-I plasma	Homo sapiens
3526 ng*h/mL	10 mg single, oral		AZILSARTAN METABOLITE M-II plasma	Homo sapiens
6350.3 ng*h/mL	5 mg single, oral		AZILSARTAN plasma	Homo sapiens
1592.7 ng*h/mL	5 mg single, oral		AZILSARTAN METABOLITE M-I plasma	Homo sapiens
1986.5 ng*h/mL	5 mg single, oral		AZILSARTAN METABOLITE M-II plasma	Homo sapiens
46688.2 ng × h/mL	80 mg single, oral	Chlorthalidone	AZILSARTAN plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
12.1 h	80 mg single, oral	Chlorthalidone	AZILSARTAN plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
1%	80 mg 1 times / day unknown, oral		AZILSARTAN plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
80 mg 1 times / day multiple, oral Recommended	unhealthy, 50.4+/-10.2	Disc. AE: Dizziness, Fatigue...
320 mg 1 times / day multiple, oral Overdose	healthy
80 mg 1 times / day multiple, oral Recommended	unhealthy	Disc. AE: Hypotension orthostatic...

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AEs

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AE	Significance	Dose	Population
Fatigue	2.79% Disc. AE	80 mg 1 times / day multiple, oral Recommended	unhealthy, 50.4+/-10.2
Dizziness	3.35% Disc. AE	80 mg 1 times / day multiple, oral Recommended	unhealthy, 50.4+/-10.2
Hypotension orthostatic	0.4% Disc. AE	80 mg 1 times / day multiple, oral Recommended	unhealthy

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1,587 substrate 1,737 inducer 781	inhibitor 1,767 substrate 1,037	inhibitor 1,852 substrate 1,217	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524 CYP2B6 810 CYP2C8 911 CYP2C19 1,478 CYP2E1 882 CYP1A1 110 CYP2A6 707 P-gp 1,461	CYP2C8 693 CYP1A1 349 CYP1A2 1,054 CYP2A6 543 CYP2B6 664 CYP2C19 991 CYP2E1 667 CYP4A11 119 P-gp 1,537

Drug as perpetrator

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Target	Modality	Activity
CYP1A1 218	inhibitor 3,277	no [IC50 >100 uM]
CYP2A6 739	inhibitor 3,277	no [IC50 >100 uM]
CYP2B6 1,001	inhibitor 3,277	no [IC50 >100 uM]
CYP2C19 1,553	inhibitor 3,277	no [IC50 >100 uM]
CYP2E1 970	inhibitor 3,277	no [IC50 >100 uM]

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Drug as victim

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Target	Modality	Activity	Clinical evidence
P-gp 1,537	substrate 3,367	inconclusive
CYP2C9 1,037	substrate 3,367	major	yes (co-administration study)
CYP1A1 349	substrate 3,367	yes
CYP1A2 1,054	substrate 3,367	yes
CYP2A6 543	substrate 3,367	yes

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:68850	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68850
ChemicalBook	CB21090899	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB21090899
eMolecules	36762351	https://www.emolecules.com/cgi-bin/more?vid=36762351
eMolecules	36905408	https://www.emolecules.com/cgi-bin/more?vid=36905408
MolPort	MolPort-023-219-167	https://www.molport.com/shop/molecule-link/MolPort-023-219-167

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PubMed

Title	Date	PubMed
No data available in table

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose in adults is 80 mg taken orally once daily. Consider a starting dose of 40 mg for patients who are treated with high doses of diuretics.

Route of Administration: Oral

In Vitro Use Guide

Unknown