CANDESARTAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H20N6O3
Molecular Weight	440.454
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC1=NC2=C(N1CC3=CC=C(C=C3)C4=C(C=CC=C4)C5=NN=NN5)C(=CC=C2)C(O)=O

InChI

InChIKey=HTQMVQVXFRQIKW-UHFFFAOYSA-N

InChI=1S/C24H20N6O3/c1-2-33-24-25-20-9-5-8-19(23(31)32)21(20)30(24)14-15-10-12-16(13-11-15)17-6-3-4-7-18(17)22-26-28-29-27-22/h3-13H,2,14H2,1H3,(H,31,32)(H,26,27,28,29)

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020838s039lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.japsonline.com/admin/php/uploads/290_pdf.pdf

Candesartan is classified as an angiotensin II receptor type 1 antagonist. Candesartan is an orally active lipophilic drug and possesses rapid oral absorption. It causes a reduction in blood pressure and is used in the treatment of hypertension. It is also used in the treatment of congestive heart failure and given as prophylaxis to reduce the severity and duration of migraine. Candesartan cilexetil, a prodrug of Candesartan, is available in the market under the trade names Atacand, Amias. Candesartan cilexetil is rapidly converted to candesartan, its active metabolite, during absorption from the gastrointestinal tract. Candesartan confers blood pressure lowering effects by antagonizing the hypertensive effects of angiotensin II via the RAAS (renin–angiotensin–aldosterone system). RAAS is a homeostatic mechanism for regulating hemodynamics, water, and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from granular cells of the juxtaglomerular apparatus in the kidneys. Renin cleaves circulating angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing total peripheral resistance, increasing sodium and water reabsorption in the kidneys via aldosterone secretion, and altering the cardiovascular structure. Angiotensin II binds to two receptors: type-1 angiotensin II receptor (AT1) and type-2 angiotensin II receptor (AT2). Candesartan selectively blocks the binding of angiotensin II to AT1 in many tissues including vascular smooth muscle and the adrenal glands. This inhibits the AT1-mediated vasoconstrictive and aldosterone-secreting effects of angiotensin II and results in an overall decrease in blood pressure. Candesartan is greater than 10,000 times more selective for AT1 than AT2.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Type-1 angiotensin II receptor 39 Target ID: CHEMBL227 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020838s039lbl.pdf	Antagonist 2737

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 546 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020838s039lbl.pdf	Primary		Approved 8307	ATACAND Approved Use Candesartan Cilexetil Tablets are an angiotensin II receptor blocker (ARB) indicated for: •Treatment of hypertension in adults and children 1 to < 17 years of age (1.1). •Treatment of heart failure (NYHA class II-IV); candesartan cilexetil tablets reduces cardiovascular death and heart failure hospitalization (1.2). 1.1 Hypertension Candesartan cilexetil tablets are indicated for the treatment of hypertension in adults and children 1 to < 17 years of age. It may be used alone or in combination with other antihypertensive agents. 1.2 Heart Failure Candesartan cilexetil tablets is indicated for the treatment of heart failure (NYHA class II-IV) in adults with left ventricular systolic dysfunction (ejection fraction ≤ 40%) to reduce cardiovascular death and to reduce heart failure hospitalizations [see CLINICAL STUDIES (14.2) Launch Date 8.9691842E11
Heart failure 87 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020838s039lbl.pdf	Primary		Approved 8307	ATACAND Approved Use Candesartan Cilexetil Tablets are an angiotensin II receptor blocker (ARB) indicated for: •Treatment of hypertension in adults and children 1 to < 17 years of age (1.1). •Treatment of heart failure (NYHA class II-IV); candesartan cilexetil tablets reduces cardiovascular death and heart failure hospitalization (1.2). 1.1 Hypertension Candesartan cilexetil tablets are indicated for the treatment of hypertension in adults and children 1 to < 17 years of age. It may be used alone or in combination with other antihypertensive agents. 1.2 Heart Failure Candesartan cilexetil tablets is indicated for the treatment of heart failure (NYHA class II-IV) in adults with left ventricular systolic dysfunction (ejection fraction ≤ 40%) to reduce cardiovascular death and to reduce heart failure hospitalizations [see CLINICAL STUDIES (14.2) Launch Date 8.9691842E11

C_max

Value	Dose	Analyte	Population
92 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10192757	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CANDESARTAN CILEXETIL serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
61 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10192757	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CANDESARTAN CILEXETIL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
79 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10192757	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	CANDESARTAN CILEXETIL serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
55 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10192757	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	CANDESARTAN CILEXETIL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1152 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10192757	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CANDESARTAN CILEXETIL serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
509 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10192757	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CANDESARTAN CILEXETIL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1359 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10192757	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	CANDESARTAN CILEXETIL serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
485 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10192757	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	CANDESARTAN CILEXETIL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
15.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10192757	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CANDESARTAN CILEXETIL serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10192757	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CANDESARTAN CILEXETIL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10192757	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	CANDESARTAN CILEXETIL serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10192757	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	CANDESARTAN CILEXETIL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020838s041lbl.pdf	unknown, unknown		CANDESARTAN CILEXETIL plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
16 mg 1 times / day steady, oral Recommended Dose: 16 mg, 1 times / day Route: oral Route: steady Dose: 16 mg, 1 times / day Co-administed with:: amlodipine(10 mg/day) Sources: https://pubmed.ncbi.nlm.nih.gov/11141435	unhealthy, 41 years n = 1 Health Status: unhealthy Age Group: 41 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/11141435	Disc. AE: Hepatitis... AEs leading to discontinuation/dose reduction: Hepatitis (acute, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/11141435
32 mg 1 times / day steady, oral Highest studied dose Dose: 32 mg, 1 times / day Route: oral Route: steady Dose: 32 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12502672	unhealthy, 59 years n = 6 Health Status: unhealthy Condition: Type 2 Diabetes Age Group: 59 years Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/12502672	Sources: https://pubmed.ncbi.nlm.nih.gov/12502672
23 mg 1 times / day steady, oral (mean) Recommended Dose: 23 mg, 1 times / day Route: oral Route: steady Dose: 23 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf	unhealthy, 67 years n = 207 Health Status: unhealthy Condition: heart failure Age Group: 67 years Sex: M+F Population Size: 207 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf	Disc. AE: Hypotension, Hyperkalemia... AEs leading to discontinuation/dose reduction: Hypotension (4.1%) Hyperkalemia (2.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf
16 mg 1 times / day steady, oral Recommended Dose: 16 mg, 1 times / day Route: oral Route: steady Dose: 16 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf	Other AEs: Disorder fetal... Other AEs: Disorder fetal Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf
2 mg 1 times / day steady, oral Dose: 2 mg, 1 times / day Route: oral Route: steady Dose: 2 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf	unhealthy n = 2350 Health Status: unhealthy Population Size: 2350 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf	Disc. AE: Headache, Dizziness... AEs leading to discontinuation/dose reduction: Headache (0.6%) Dizziness (0.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf

AEs

AE	Significance	Dose	Population
Hepatitis	acute, 1 patient Disc. AE	16 mg 1 times / day steady, oral Recommended Dose: 16 mg, 1 times / day Route: oral Route: steady Dose: 16 mg, 1 times / day Co-administed with:: amlodipine(10 mg/day) Sources: https://pubmed.ncbi.nlm.nih.gov/11141435	unhealthy, 41 years n = 1 Health Status: unhealthy Age Group: 41 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/11141435
Hyperkalemia	2.4% Disc. AE	23 mg 1 times / day steady, oral (mean) Recommended Dose: 23 mg, 1 times / day Route: oral Route: steady Dose: 23 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf	unhealthy, 67 years n = 207 Health Status: unhealthy Condition: heart failure Age Group: 67 years Sex: M+F Population Size: 207 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf
Hypotension	4.1% Disc. AE	23 mg 1 times / day steady, oral (mean) Recommended Dose: 23 mg, 1 times / day Route: oral Route: steady Dose: 23 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf	unhealthy, 67 years n = 207 Health Status: unhealthy Condition: heart failure Age Group: 67 years Sex: M+F Population Size: 207 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf
Disorder fetal		16 mg 1 times / day steady, oral Recommended Dose: 16 mg, 1 times / day Route: oral Route: steady Dose: 16 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf
Dizziness	0.3% Disc. AE	2 mg 1 times / day steady, oral Dose: 2 mg, 1 times / day Route: oral Route: steady Dose: 2 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf	unhealthy n = 2350 Health Status: unhealthy Population Size: 2350 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf
Headache	0.6% Disc. AE	2 mg 1 times / day steady, oral Dose: 2 mg, 1 times / day Route: oral Route: steady Dose: 2 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf	unhealthy n = 2350 Health Status: unhealthy Population Size: 2350 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020838s036lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3347	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3347
ChemicalBook	CB0209324	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0209324
MolPort	MolPort-003-845-570	https://www.molport.com/shop/molecule-link/MolPort-003-845-570
MolPort	MolPort-005-943-739	https://www.molport.com/shop/molecule-link/MolPort-005-943-739
Selleck Chemicals	Candesartan(Atacand)	http://www.selleckchem.com/products/Candesartan(Atacand).html
ZINC	ZINC000003782818	http://zinc15.docking.org/substances/ZINC000003782818
eMolecules	32278092	https://www.emolecules.com/cgi-bin/more?vid=32278092
eMolecules	901501	https://www.emolecules.com/cgi-bin/more?vid=901501

PubMed

Title	Date	PubMed
[Angiotensin receptor blockers--significance for the therapy of hypertension].	2001	11450162
The comparative pharmacology of angiotensin II receptor antagonists.	2001	11333013
The effect duration of candesartan cilexetil once daily, in comparison with enalapril once daily, in patients with mild to moderate hypertension.	2001	11332334
Antihypertensive treatment in elderly patients aged 75 years or over: a 24-week study of the tolerability of candesartan cilexetil in relation to hydrochlorothiazide.	2001	11302289
Effects of quinapril on expression of eNOS, ACE, and AT1 receptor in deoxycorticosterone acetate-salt hypertensive rats.	2001 Apr	11336177
Comparison of candesartan versus enalapril in essential hypertension. Italian Candesartan Study Group.	2001 Feb	11243303
Angiotensin II type 1 receptor blockers.	2001 Feb 13	11171802
ACE inhibitor and AT1 antagonist blockade of deformation-induced gene expression in the rabbit jugular vein through B2 receptor activation.	2001 Jan	11145934
Antihypertensive efficacy of candesartan in comparison to losartan: the CLAIM study.	2001 Jan-Feb	11416677
In vitro and in vivo pharmacology of olmesartan medoxomil, an angiotensin II type AT1 receptor antagonist.	2001 Jun	11451212
The influence of chronic antihypertensive treatment on the central pressor response in SHR.	2001 Mar	11325077
Effects of AT1 receptor antagonist on proteoglycan gene expression in hypertensive rats.	2001 Mar	11325076
Lithium intoxication after administration of AT1 blockers.	2001 Mar	11305712
Perceived benefit after participating in positive or negative/neutral heart failure trials: the patients' perspective.	2001 Mar	11246060
Combination treatment effective option for hypertensive, diabetic patients with microalbuminuria.	2001 Mar 20	11276560
Angiotensin type 1 receptor antagonism and ACE inhibition produce similar renoprotection in N(omega)-nitro-L>-arginine methyl ester/spontaneously hypertensive rats.	2001 May	11358938
[Change from ACE inhibitor, Ca-antagonist or beta-blocker to candesartan cilexetil: better efficacy and tolerance. SWITCH study (German study segment)].	2001 May 11	11402910
Tight binding of the angiotensin AT(1) receptor antagonist.	2001 May 15	11322926
Reliability, validity, and responsiveness of the six-minute walk test in patients with heart failure.	2001 Oct	11579362
Autoregulated glomerular filtration rate during candesartan treatment in hypertensive type 2 diabetic patients.	2001 Oct	11576357

Patents

Sample Use Guides

In Vivo Use Guide

Adult Hypertension: 2 DOSAGE AND ADMINISTRATION 2.1 Adult Hypertension The usual recommended starting dose of ATACAND (candesartan cilexetil) is 16 mg once daily when it is used as monotherapy in patients who are not volume depleted. ATACAND can be administered once or twice daily with total daily doses ranging from 8 mg to 32 mg. Pediatric Hypertension 1 to < 17 Years of Age: Children 1 to < 6 years of age: The dose range is 0.05 to 0.4 mg/kg per day. The recommended starting dose is 0.20 mg/kg (oral suspension). Children 6 to < 17 years of age: For those less than 50 kg, the dose range is 2 to 16 mg per day. The recommended starting dose is 4 to 8 mg. For those greater than 50 kg, the dose range is 4 to 32 mg per day. The recommended starting dose is 8 to 16 mg. Adult Heart Failure: The recommended initial dose for treating heart failure is 4 mg once daily. The target dose is 32 mg once daily, which is achieved by doubling the dose at approximately 2-week intervals, as tolerated by the patient.

Route of Administration: Oral

In Vitro Use Guide

Primary cultures of human retinal endothelial cells (EC) were candesartan treatment (1μg/ml).

Name

Type

Language

CANDESARTAN

Official Name

English

Candesartan [WHO-DD]

Common Name

English

CV-11974

Code

English

CANDESARTAN [VANDF]

Common Name

English

CANDESARTAN [USAN]

Common Name

English

NSC-759858

Code

English

BLOPRESS

Brand Name

English

CANDESARTAN [MI]

Common Name

English

CANDESARTAN CILEXETIL RELATED COMPOUND G

Common Name

English

candesartan [INN]

Common Name

English

CANDEMORE

Brand Name

English

CANDESARTAN CILEXETIL RELATED COMPOUND G [USP-RS]

Common Name

English

CANDESARTAN [HSDB]

Common Name

English

1H-BENZIMIDAZOLE-7-CARBOXYLIC ACID, 2-ETHOXY-1-((2'-(1H-TETRAZOL-5-YL)(1,1'-BIPHENYL)-4-YL)METHYL)-

Common Name

English

CANDESARTAN CILEXETIL IMPURITY G [EP IMPURITY]

Common Name

English

2-ETHOXY-1-(P-(O-1H-TETRAZOL-5-YLPHENYL)BENZYL)-7-BENZIMIDAZOLECARBOXYLIC ACID

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC09DB07