U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C22H23ClN6O
Molecular Weight 422.9114
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOSARTAN

SMILES

CCCCc1nc(c(CO)n1Cc2ccc(cc2)-c3ccccc3-c4n[nH]nn4)Cl

InChI

InChIKey=PSIFNNKUMBGKDQ-UHFFFAOYSA-N
InChI=1S/C22H23ClN6O/c1-2-3-8-20-24-21(23)19(14-30)29(20)13-15-9-11-16(12-10-15)17-6-4-5-7-18(17)22-25-27-28-26-22/h4-7,9-12,30H,2-3,8,13-14H2,1H3,(H,25,26,27,28)

HIDE SMILES / InChI
Losartan is a selective, competitive angiotensin II receptor type 1 (AT1) antagonist. Losartant is recommended as one of several preferred agents for the initial management of hypertension. Administration of losartan reduces the risk of stroke in patients with hypertension and left ventricular hypertrophy. Losartan is indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria in patients with type 2 diabetes and a history of hypertension.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
4.0 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
COZAAR

Approved Use

Angiotensin II receptor antagonists are recommended as one of several preferred agents for the initial management of hypertension; other options include ACE inhibitors, calcium-channel blockers, and thiazide diuretics. While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes. Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).

Launch Date

7.9781757E11
Preventing
COZAAR

Approved Use

Preliminary evidence suggests that aspirin therapy at baseline in patients receiving losartan may reduce the risk of combined cardiovascular death, stroke, and acute MI compared with aspirin therapy at baseline in patients receiving atenolol, but there is evidence that this benefit does not apply to Black patients.

Launch Date

7.9781757E11
Primary
COZAAR

Approved Use

Management of diabetic nephropathy manifested by elevated Scr and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes mellitus and hypertension.

Launch Date

7.9781757E11
Primary
COZAAR

Approved Use

Angiotensin II receptor antagonists are considered a reasonable alternative for inhibition of the renin-angiotensin system in patients with heart failure and reduced left ventricular ejection fraction (LVEF) who are intolerant of ACE inhibitors; because of their established benefits, ACE inhibitors are preferred.

Launch Date

7.9781757E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
224 ng/mL
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LOSARTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
442 ng × h/mL
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LOSARTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.1 h
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LOSARTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1.3%
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LOSARTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
minor
minor
minor
minor
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: coadministration with fluconazole (CYP2C9 inhibitor) increased AUC24 by 66%; coadministration with phenytoin (CYP2C9 inducer) increased AUC24 of drug by 17% and 29% in those with CYP2C9*1/*1 genotype;
Page: 2,8
yes
yes (co-administration study)
Comment: coadministration with ketoconazole or erythromycin (CYP3A4 inhibitors) had no effect on AUC24 of drug; coadministration with rifampin (CYP3A4 inducer) increased AUC24 of drug by 35%;
Page: 2.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
The cost-effectiveness of losartan versus captopril in patients with symptomatic heart failure.
1999
Arterial function in nitric oxide-deficient hypertension: influence of long-term angiotensin II receptor antagonism.
1999 Jun
Effects of beta-receptor blockade and angiotensin II type I receptor antagonism in isoproterenol-induced heart failure in the rat.
1999 Nov-Dec
Angiotensin II stimulates intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells and increases soluble ICAM-1 release in vivo.
1999 Oct 12
EXP3174, the AII antagonist human metabolite of losartan, but not losartan nor the angiotensin-converting enzyme inhibitor captopril, prevents the development of lethal ischemic ventricular arrhythmias in a canine model of recent myocardial infarction.
1999 Sep
Randomised comparison of losartan vs. captopril on quality of life in elderly patients with symptomatic heart failure: the losartan heart failure ELITE quality of life substudy.
2000
Neuropeptide Y enhances potassium excretion by mechanisms distinct from those controlling sodium excretion.
2000 Feb
Angiotensin II receptor blockade unmasks a depressor response to endothelin antagonists in rats.
2000 Mar-Apr
First dose hypotension after angiotensin converting enzyme inhibitor captopril and angiotensin II blocker losartan in patients with acute myocardial infarction.
2000 Sep 15
Intrarenal renin-angiotensin system contributes to tubular acidification adaptation following uninephrectomy.
2001
Atypical angiotensin receptors may mediate water intake induced by central injections of angiotensin II and of serotonin in pigeons.
2001 Apr 20
Angiotensin II induces migration and Pyk2/paxillin phosphorylation of human monocytes.
2001 Feb
Role of endothelin and isoprostanes in slow pressor responses to angiotensin II.
2001 Feb
Angiotensin II relaxes microvessels via the AT(2) receptor and Ca(2+)-activated K(+) (BK(Ca)) channels.
2001 Feb
Combined therapy with an angiotensin II receptor blocker and an angiotensin-converting enzyme inhibitor in heart failure.
2001 Feb
Angiotensin II is involved in nitric oxide synthase and cyclo-oxygenase inhibition-induced leukocyte-endothelial cell interactions in vivo.
2001 Feb
Hyperoxia/normoxia-driven retinal angiogenesis in mice: a role for angiotensin II.
2001 Feb
Angiotensin II type 1 receptor blockers.
2001 Feb 13
Comparative effect of ace inhibition and angiotensin II type 1 receptor antagonism on bioavailability of nitric oxide in patients with coronary artery disease: role of superoxide dismutase.
2001 Feb 13
Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy.
2001 Feb 13
Losartan versus enalapril on cerebral edema and proteinuria in stroke-prone hypertensive rats.
2001 Jan
Relation of left ventricular geometry and function to systemic hemodynamics in hypertension: the LIFE Study. Losartan Intervention For Endpoint Reduction in Hypertension Study.
2001 Jan
Renal and vascular injury induced by exogenous angiotensin II is AT1 receptor-dependent.
2001 Jan
Angiotensin signaling and receptor types in teleost fish.
2001 Jan
Increased AT(1) receptor expression and mRNA in kidney glomeruli of AT(2) receptor gene-disrupted mice.
2001 Jan
Losartan, an angiotensin type I receptor antagonist, improves conduit vessel endothelial function in Type II diabetes.
2001 Jan
Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan.
2001 Jan 16
A kinetic model for the metabolic interaction of two substrates at the active site of cytochrome P450 3A4.
2001 Jan 19
Mitogen-activated protein kinase activity regulation role of angiotensin and endothelin systems in vascular smooth muscle cells.
2001 Jan 5
Mannitol-induced toxicity in a diabetic patient receiving losartan.
2001 Mar
Effect of angiotensin II on venodilator response to nitroglycerin.
2001 Mar
Identification, distribution, and expression of angiotensin II receptors in the normal human prostate and benign prostatic hyperplasia.
2001 Mar
AT(1) receptor blockers prevent sympathetic hyperactivity and hypertension by chronic ouabain and hypertonic saline.
2001 Mar
Are angiotensin II receptor blockers more efficacious than placebo in heart failure? Implications of ELITE-2. Evaluation of Losartan In The Elderly.
2001 Mar 1
The role of angiotensin receptor blockers in the management of chronic heart failure.
2001 Mar 12
Losartan reduces hematocrit in patients with chronic obstructive pulmonary disease and secondary erythrocytosis.
2001 Mar 6
Patents

Sample Use Guides

For treatment of hypertension, Joint National Committee (JNC) 8 expert panel recommends initial dosage of 50 mg daily and target dosage of 100 mg daily (given in 1 dose or 2 divided doses) based on dosages used in randomized controlled studies.
Route of Administration: Oral
From 30 to 40 min after confirmation of endothelium removal, the test compounds were incubated at a concentration of 0.1 uM. After an incubation period of 20 or 60 min, aortic preparations were treated with AII, using 3-fold increasing concentrations from 0.1 nM to 1 uM. Kb for binding with angiotensin receptor was 4 nM with 20 min incubation, and 9 nM with 60 min incubation.
Name Type Language
LOSARTAN
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
NSC-758699
Code English
ALLISARTAN
Brand Name English
LOSARTAN [MI]
Common Name English
LOZAP
Brand Name English
1H-IMIDAZOLE-5-METHANOL, 2-BUTYL-4-CHLORO-1-((2'-(1H-TETRAZOL-5-YL)(1,1'-BIPHENYL)-4-YL)METHYL)-
Systematic Name English
ANGIZAAR
Brand Name English
LOSARTAN [INN]
Common Name English
2-BUTYL-4-CHLORO-1-(P-(O-1H-TETRAZOL-5-YLPHENYL)BENZYL)IMIDAZOLE-5-METHANOL
Common Name English
HGP1405
Code English
HGP-1405
Code English
DUP-89
Common Name English
LOSARTIC
Brand Name English
LOSARTAN [VANDF]
Common Name English
LOSARTAN [WHO-DD]
Common Name English
Classification Tree Code System Code
NDF-RT N0000000070
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
FDA ORPHAN DRUG 357211
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
LIVERTOX 573
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
NCI_THESAURUS C66930
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
WHO-ATC C09DA01
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
WHO-VATC QC09DA01
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
NDF-RT N0000175561
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
WHO-VATC QC09DB06
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
WHO-ATC C09CA01
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
FDA ORPHAN DRUG 668618
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
EU-Orphan Drug EU/3/19/2142
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
WHO-VATC QC09CA01
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
WHO-ATC C09DB06
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
Code System Code Type Description
RXCUI
52175
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY RxNorm
FDA UNII
JMS50MPO89
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
HSDB
7043
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
CAS
114798-26-4
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
DRUG CENTRAL
1610
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
WIKIPEDIA
LOSARTAN
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
DRUG BANK
DB00678
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
IUPHAR
590
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
ChEMBL
CHEMBL191
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
EVMPD
SUB32953
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
ALTERNATIVE
LACTMED
Losartan
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
EVMPD
SUB08593MIG
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
NCI_THESAURUS
C66869
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
EPA CompTox
114798-26-4
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
INN
6913
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
MERCK INDEX
M6911
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY Merck Index
MESH
D019808
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY
PUBCHEM
3961
Created by admin on Fri Jun 25 21:56:30 UTC 2021 , Edited by admin on Fri Jun 25 21:56:30 UTC 2021
PRIMARY