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

Details

Stereochemistry ACHIRAL
Molecular Formula C22H23ClN6O
Molecular Weight 422.911
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOSARTAN

SMILES

CCCCC1=NC(Cl)=C(CO)N1CC2=CC=C(C=C2)C3=C(C=CC=C3)C4=NN=NN4

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

Molecular Formula C22H23ClN6O
Molecular Weight 422.911
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
A comparison of the angiotensin II antagonists valsartan and losartan in the treatment of essential hypertension.
1999 Apr
The effects of fluvastatin, a CYP2C9 inhibitor, on losartan pharmacokinetics in healthy volunteers.
1999 Apr
Losartan: a study of pharmacovigilance data on 14,522 patients.
1999 Aug
2-Tetradecylglycidic acid, an inhibitor of carnitine palmitoyltransferase-1, induces myocardial hypertrophy via the AT1 receptor.
1999 Aug
Angioedema due to losartan.
1999 Jan
Brain renin-angiotensin system and ouabain-induced sympathetic hyperactivity and hypertension in Wistar rats.
1999 Jul
Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension.
1999 Jul 9
Increased efficacy and tolerability with losartan plus hydrochlorothiazide in patients with uncontrolled hypertension and therapy-related symptoms receiving two monotherapies.
1999 Sep-Oct
[Prospects of endothelial dysfunction reversion in patients with congestive heart failure].
2000
Modulation of apoptotic and inflammatory genes by bioflavonoids and angiotensin II inhibition in ureteral obstruction.
2000 Aug 1
Meta-analysis of observed mortality data from all-controlled, double-blind, multiple-dose studies of losartan in heart failure. Losartan Heart Failure Mortality Meta-analysis Study Group.
2000 Jan 15
Losartan: a review of its use, with special focus on elderly patients.
2000 Mar
Long-term central hemodynamic effects at rest and during exercise of losartan in essential hypertension.
2000 Oct
First dose hypotension after angiotensin converting enzyme inhibitor captopril and angiotensin II blocker losartan in patients with acute myocardial infarction.
2000 Sep 15
The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure.
2001 Apr
Angiotensin II stimulates cardiac L-type Ca(2+) current by a Ca(2+)- and protein kinase C-dependent mechanism.
2001 Apr
Tonic suppression of spontaneous baroreceptor reflex by endogenous angiotensins via AT(2) subtype receptors at nucleus reticularis ventrolateralis in the rat.
2001 Apr
Expression of cell cycle proteins in blood vessels of angiotensin II-infused rats: role of AT(1) receptors.
2001 Feb
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
Combined therapy with an angiotensin II receptor blocker and an angiotensin-converting enzyme inhibitor in heart failure.
2001 Feb
A two-state receptor model for the interaction between angiotensin II type 1 receptors and non-peptide antagonists.
2001 Feb 1
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
Role of the central nervous system in the development of hypertension produced by chronic nitric oxide blockade in rats.
2001 Jan
Cysteinyl leukotrienes are involved in angiotensin II-induced contraction of aorta from spontaneously hypertensive rats.
2001 Jan
Effect of angiotensin II on venodilator response to nitroglycerin.
2001 Mar
Effect of oral contraceptives on the renin angiotensin system and renal function.
2001 Mar
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.
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:13:03 UTC 2023
Edited
by admin
on Wed Jul 05 23:13:03 UTC 2023
Record UNII
JMS50MPO89
Record Status Validated (UNII)
Record Version
  • Download
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 [WHO-DD]
Common Name English
LOSARTAN [VANDF]
Common Name English
Classification Tree Code System Code
NDF-RT N0000000070
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
FDA ORPHAN DRUG 357211
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
LIVERTOX NBK547842
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
NCI_THESAURUS C66930
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
WHO-ATC C09DA01
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
WHO-VATC QC09DA01
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
NDF-RT N0000175561
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
WHO-VATC QC09DB06
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
WHO-ATC C09CA01
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
FDA ORPHAN DRUG 668618
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
EU-Orphan Drug EU/3/19/2142
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
WHO-VATC QC09CA01
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
WHO-ATC C09DB06
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
Code System Code Type Description
RXCUI
52175
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY RxNorm
FDA UNII
JMS50MPO89
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
HSDB
7043
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
CHEBI
6541
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
CAS
114798-26-4
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
DRUG CENTRAL
1610
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
WIKIPEDIA
LOSARTAN
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
DRUG BANK
DB00678
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
IUPHAR
590
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
ChEMBL
CHEMBL191
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
EVMPD
SUB32953
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
ALTERNATIVE
LACTMED
Losartan
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
EVMPD
SUB08593MIG
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
CHEBI
149504
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
DAILYMED
JMS50MPO89
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
NCI_THESAURUS
C66869
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
NSC
758699
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
EPA CompTox
DTXSID7023227
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
INN
6913
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
SMS_ID
100000082055
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
MERCK INDEX
M6911
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY Merck Index
MESH
D019808
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
PUBCHEM
3961
Created by admin on Wed Jul 05 23:13:04 UTC 2023 , Edited by admin on Wed Jul 05 23:13:04 UTC 2023
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
IC50
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
Liver concentrations were estimated to be about 50 micromolar. this indicates that Losartan might inhibit the AA metabolism in the liver.
IC50
SALT/SOLVATE -> PARENT
DERIVATIVE -> PARENT
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
TRANSPORTER -> INHIBITOR
Related Record Type Details
IMPURITY -> PARENT
NMBA is a priority toxic pollutant. FDA is temporarily not objecting to Losartan with NMBA below 9.82 ppm remaining on the market.
IMPURITY -> PARENT
Acceptable intake level of NDEA in ppm.
IMPURITY GENOTOXIC->PARENT
NDMA is an organic chemical that is part of a family of potent carcinogens.
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC Elimination
PHARMACOKINETIC