LOSARTAN

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 Search

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

Description
Sources: https://www.drugs.com/monograph/cozaar.html

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Angiotensin II receptor 9 Target ID: CHEMBL2094256 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16610806	Antagonist 2778		4.0 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 567 Sources: https://www.drugs.com/monograph/cozaar.html	Primary	Phase IV 63	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
Stroke 144 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020386s060lbl.pdf	Preventing	Phase IV 63	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
Diabetic nephropathy 35 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020386s060lbl.pdf	Primary	Approved 8429	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
Heart failure 103 Sources: https://www.drugs.com/monograph/cozaar.html	Primary	Approved 8429	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

C_max

Value	Dose	Co-administered	Analyte	Population
224 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020386s062lbl.pdf	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

Value	Dose	Co-administered	Analyte	Population
442 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020386s062lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.1 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020386s062lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
1.3% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020386s062lbl.pdf	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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882 P-gp 1461 PEPT1 20 MRP4 204 OAT4 146 OAT1 599 OAT3 642	P-gp 1537 OATP2B1 104 UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A5 55 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A9 380 UGT1A10 291 UGT2B4 249 UGT2B7 389 UGT2B10 127 UGT2B15 203 UGT2B17 213 UGT2B28 63

Drug as perpetrator

Target	Modality	Activity
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	moderate [IC50 138 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	no
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	no
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	slight
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	weak [IC50 210 uM]
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17674156/	yes [IC50 1.5 uM]
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17674156/	yes [IC50 1.6 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17674156/	yes [IC50 12 uM]
OAT4 146	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17674156/	yes [IC50 18 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	yes [IC50 524 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	yes [IC50 81 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20222053/ Page: 6.0	yes [IC50 >100 uM]
PEPT1 22	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18824524/	yes [Ki 24 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	minor
UGT1A7 236	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	minor
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	minor
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	minor
UGT1A5 55	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	no
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	no
UGT2B10 127	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	no
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	no
UGT2B28 63	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	no
UGT2B4 249	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	no
OATP2B1 104	substrate 3367 Sources: https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.24.1_supplement.758.2	yes
P-gp 1537	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571937/	yes
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	yes
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	yes
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	yes
UGT2B17 213	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	yes
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	yes
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16029066/ Page: 2,8	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 CYP2C91/1 genotype; Sources: https://pubmed.ncbi.nlm.nih.gov/16029066/ Page: 2,8
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16029066/ Page: 2.0	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%; Sources: https://pubmed.ncbi.nlm.nih.gov/16029066/ Page: 2.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/10715269/ Page: 4.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6541	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6541
ChemicalBook	CB02485742	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB02485742
ChemicalBook	CB32545285	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB32545285
ChemicalBook	CB72485741	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB72485741
ChemicalBook	CB8120081	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8120081
MolPort	MolPort-003-666-553	https://www.molport.com/shop/molecule-link/MolPort-003-666-553
MolPort	MolPort-006-167-607	https://www.molport.com/shop/molecule-link/MolPort-006-167-607
ZINC	ZINC000003873160	http://zinc15.docking.org/substances/ZINC000003873160
eMolecules	601417	https://www.emolecules.com/cgi-bin/more?vid=601417

PubMed

Title	Date	PubMed
Effects of losartan on ventricular remodeling in experimental infarction in rats.	2000 Dec	11175471
[Acute kidney failure and losartan: a recently observed event of antagonists of angiotensin II AT1 receptors].	2000 Sep	11227361
The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure.	2001 Apr	11247801
Angiotensin II stimulates cardiac L-type Ca(2+) current by a Ca(2+)- and protein kinase C-dependent mechanism.	2001 Apr	11247763
Tonic suppression of spontaneous baroreceptor reflex by endogenous angiotensins via AT(2) subtype receptors at nucleus reticularis ventrolateralis in the rat.	2001 Apr	11170225
Atypical angiotensin receptors may mediate water intake induced by central injections of angiotensin II and of serotonin in pigeons.	2001 Apr 20	11231042
Left ventricular hypertrophy and angiotensin II antagonists.	2001 Feb	11243310
Angiotensin II increases vesicular trafficking in brain neurons.	2001 Feb	11230355
Expression of cell cycle proteins in blood vessels of angiotensin II-infused rats: role of AT(1) receptors.	2001 Feb	11230342
Angiotensin II induces migration and Pyk2/paxillin phosphorylation of human monocytes.	2001 Feb	11230339
Role of endothelin and isoprostanes in slow pressor responses to angiotensin II.	2001 Feb	11230326
Angiotensin II relaxes microvessels via the AT(2) receptor and Ca(2+)-activated K(+) (BK(Ca)) channels.	2001 Feb	11230289
Mortality after coronary artery occlusion in different models of cardiac hypertrophy in rats.	2001 Feb	11230273
Role of angiotensin II in altered baroreflex function of conscious rabbits during late pregnancy.	2001 Feb	11228506
Modulation of alveolar-capillary sodium handling as a mechanism of protection of gas transfer by enalapril, and not by losartan, in chronic heart failure.	2001 Feb	11216953
Combined therapy with an angiotensin II receptor blocker and an angiotensin-converting enzyme inhibitor in heart failure.	2001 Feb	11215846
DNA damage of lymphocytes in experimental chronic renal failure: beneficial effects of losartan.	2001 Feb	11169013
Different effects of angiotensin II and catecholamine on renal cell apoptosis and proliferation in rats.	2001 Feb	11168946
A two-state receptor model for the interaction between angiotensin II type 1 receptors and non-peptide antagonists.	2001 Feb 1	11172731
Angiotensin II type 1 receptor blockers.	2001 Feb 13	11171802
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	11171786
Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy.	2001 Feb 13	11171784
Acute administration of nicotine impairs the hypotensive responses to bradykinin in rats.	2001 Feb 16	11226399
Losartan and fetal toxic effects.	2001 Feb 3	11211003
[Well tolerated sartans. More normal blood pressure finally?].	2001 Feb 8	11247370
[Treating not only blood pressure. Advantages for microcirculation].	2001 Feb 8	11247369
Acute effects of E-3174, a human active metabolite of losartan, on the cardiovascular system in tachycardia-induced canine heart failure.	2001 Jan	11213032
Role of the central nervous system in the development of hypertension produced by chronic nitric oxide blockade in rats.	2001 Jan	11213029
Contribution of angiotensin II, endothelin 1 and the endothelium to the slow inotropic response to stretch in ferret papillary muscle.	2001 Jan	11212215
Functional expression of angiotensin II receptors in type-I cells of the rat carotid body.	2001 Jan	11212210
Losartan versus enalapril on cerebral edema and proteinuria in stroke-prone hypertensive rats.	2001 Jan	11206680
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	11204292
New competition in the realm of renin-angiotensin axis inhibition; the angiotensin II receptor antagonists in congestive heart failure.	2001 Jan	11197588
Renal and vascular injury induced by exogenous angiotensin II is AT1 receptor-dependent.	2001 Jan	11174028
Angiotensin II inhibits rat arterial KATP channels by inhibiting steady-state protein kinase A activity and activating protein kinase Ce.	2001 Jan 15	11208968
Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan.	2001 Jan 16	11208681
Central interactions between angiotensin II and PGD(2) in the regulation of vasopressin and oxytocin secretion in dehydrated rats.	2001 Jan 19	11166690
Mannitol-induced toxicity in a diabetic patient receiving losartan.	2001 Mar	11247599
Restoration of normal ventricular electrophysiology in renovascular hypertensive rabbits after treatment with losartan.	2001 Mar	11243422
Effect of angiotensin II on venodilator response to nitroglycerin.	2001 Mar	11240977
MK-954 (losartan potassium) exerts endothelial protective effects against reperfusion injury: evidence of an e-NOS mRNA overexpression after global ischemia.	2001 Mar	11223426
Identification, distribution, and expression of angiotensin II receptors in the normal human prostate and benign prostatic hyperplasia.	2001 Mar	11181554
AT(1) receptor blockers prevent sympathetic hyperactivity and hypertension by chronic ouabain and hypertonic saline.	2001 Mar	11179079
Effect of oral contraceptives on the renin angiotensin system and renal function.	2001 Mar	11171661
Cerebral Na concentration, Na appetite and thirst of sheep: influence of somatostatin and losartan.	2001 Mar	11171646
Glucocorticoid modulation of cardiovascular and autonomic function in preterm lambs: role of ANG II.	2001 Mar	11171641
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	11230847
Effect of losartan on degree of mitral regurgitation quantified by echocardiography.	2001 Mar 1	11230841
The role of angiotensin receptor blockers in the management of chronic heart failure.	2001 Mar 12	11231698
Losartan reduces hematocrit in patients with chronic obstructive pulmonary disease and secondary erythrocytosis.	2001 Mar 6	11242510

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

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