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

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

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 2737		4.0 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 546 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 143 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 8307	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 87 Sources: https://www.drugs.com/monograph/cozaar.html	Primary	Approved 8307	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 1670 inhibitor 1532	substrate 985 inhibitor 1695	inhibitor 1789	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2A6 670 CYP2C19 1410 CYP2E1 846 P-gp 1401 PEPT1 20 MRP4 202 OAT4 145 OAT1 584 OAT3 625	P-gp 1491 OATP2B1 103 UGT1A1 417 UGT1A3 421 UGT1A4 345 UGT1A5 55 UGT1A6 306 UGT1A7 235 UGT1A8 282 UGT1A9 378 UGT1A10 289 UGT2B4 248 UGT2B7 387 UGT2B10 127 UGT2B15 202 UGT2B17 212 UGT2B28 63

Drug as perpetrator

Target	Modality	Activity
CYP2C19 1484	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	moderate [IC50 138 uM]
CYP2D6 1826	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	no
CYP2E1 929	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	no
CYP2A6 702	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	slight
CYP3A4 1857	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	weak [IC50 210 uM]
MRP4 235	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/17674156/	yes [IC50 1.5 uM]
OAT3 627	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/17674156/	yes [IC50 1.6 uM]
OAT1 588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/17674156/	yes [IC50 12 uM]
OAT4 145	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/17674156/	yes [IC50 18 uM]
CYP1A2 1620	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	yes [IC50 524 uM]
CYP2C9 1747	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0	yes [IC50 81 uM]
P-gp 1588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/20222053/ Page: 6.0	yes [IC50 >100 uM]
PEPT1 22	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/18824524/	yes [Ki 24 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT1A4 345	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	minor
UGT1A7 235	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	minor
UGT1A8 282	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	minor
UGT1A9 378	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	minor
UGT1A5 55	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	no
UGT1A6 306	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	no
UGT2B10 127	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	no
UGT2B15 202	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	no
UGT2B28 63	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	no
UGT2B4 248	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	no
OATP2B1 103	substrate 3264 Sources: https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.24.1_supplement.758.2	yes
P-gp 1491	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571937/	yes
UGT1A1 417	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	yes
UGT1A10 289	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	yes
UGT1A3 421	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	yes
UGT2B17 212	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	yes
UGT2B7 387	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18674515/	yes
CYP2C9 985	substrate 3264 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 1670	substrate 3264 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 1603	inhibitor 1584 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
The cost-effectiveness of losartan versus captopril in patients with symptomatic heart failure.	1999	10516413
Angioedema due to losartan.	1999 Sep	10492494
Losartan-induced angioedema.	1999 Sep	10492493
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	11131930
Effect of indomethacin on blood pressure lowering by captopril and losartan in hypertensive patients.	2000 Sep	10988282
Intrarenal renin-angiotensin system contributes to tubular acidification adaptation following uninephrectomy.	2001	11053982
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
Role of endothelin and isoprostanes in slow pressor responses to angiotensin II.	2001 Feb	11230326
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
Gap junction remodeling in hypertrophied left ventricles of aortic-banded rats: prevention by angiotensin II type 1 receptor blockade.	2001 Feb	11162128
Angiotensin II is involved in nitric oxide synthase and cyclo-oxygenase inhibition-induced leukocyte-endothelial cell interactions in vivo.	2001 Feb	11159720
Hyperoxia/normoxia-driven retinal angiogenesis in mice: a role for angiotensin II.	2001 Feb	11157878
Acute administration of nicotine impairs the hypotensive responses to bradykinin in rats.	2001 Feb 16	11226399
Pressure overload increases GATA4 binding activity via endothelin-1.	2001 Feb 6	11156886
Losartan versus enalapril on cerebral edema and proteinuria in stroke-prone hypertensive rats.	2001 Jan	11206680
New competition in the realm of renin-angiotensin axis inhibition; the angiotensin II receptor antagonists in congestive heart failure.	2001 Jan	11197588
Interaction between paracrine tumor necrosis factor-alpha and paracrine angiotensin II during myocardial ischemia.	2001 Jan	11153758
Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan.	2001 Jan 16	11208681
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
The role of angiotensin receptor blockers in the management of chronic heart failure.	2001 Mar 12	11231698

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 18:01:28 UTC 2022` Edited by `admin` on `Fri Dec 16 18:01:28 UTC 2022`
Record UNII	JMS50MPO89
Record Status	`Validated (UNII)`
Record Version

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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