LOSARTAN HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H23ClN6O.ClH
Molecular Weight	459.372
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=YXKZHKIWSSTSPS-UHFFFAOYSA-N

InChI=1S/C22H23ClN6O.ClH/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);1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 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 1995
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 1995
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 1995
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 1995

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
The effects of fluvastatin, a CYP2C9 inhibitor, on losartan pharmacokinetics in healthy volunteers.	1999 Apr	10197301
Hemodynamic and renal effects of indomethacin in losartan-treated hypertensive individuals.	1999 Feb	10090350
Angioedema due to losartan.	1999 Jan	10195365
Arterial function in nitric oxide-deficient hypertension: influence of long-term angiotensin II receptor antagonism.	1999 Jun	10533618
Angioedema due to losartan.	1999 Sep	10492494
Increased efficacy and tolerability with losartan plus hydrochlorothiazide in patients with uncontrolled hypertension and therapy-related symptoms receiving two monotherapies.	1999 Sep-Oct	10915394
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
[Prospects of endothelial dysfunction reversion in patients with congestive heart failure].	2000	10979640
Neuropeptide Y enhances potassium excretion by mechanisms distinct from those controlling sodium excretion.	2000 Feb	10737671
Arterial responses in vitro and plasma digoxin immunoreactivity after losartan and enalapril treatments in experimental hypertension.	2000 Jan	10720105
Losartan: a review of its use, with special focus on elderly patients.	2000 Mar	10803861
Angiotensin II receptor blockade unmasks a depressor response to endothelin antagonists in rats.	2000 Mar-Apr	10796056
Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II.	2000 May 6	10821361
First dose hypotension after angiotensin converting enzyme inhibitor captopril and angiotensin II blocker losartan in patients with acute myocardial infarction.	2000 Sep 15	11077134
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
Angiotensin II increases vesicular trafficking in brain neurons.	2001 Feb	11230355
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
Acute administration of nicotine impairs the hypotensive responses to bradykinin in rats.	2001 Feb 16	11226399
Contribution of angiotensin II, endothelin 1 and the endothelium to the slow inotropic response to stretch in ferret papillary muscle.	2001 Jan	11212215
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
ANG II potentiates mitogenic effect of norepinephrine in vascular muscle cells: role of FGF-2.	2001 Jan	11123223
Cysteinyl leukotrienes are involved in angiotensin II-induced contraction of aorta from spontaneously hypertensive rats.	2001 Jan	11121807
Losartan, an angiotensin type I receptor antagonist, improves conduit vessel endothelial function in Type II diabetes.	2001 Jan	11115412
Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan.	2001 Jan 16	11208681
Restoration of normal ventricular electrophysiology in renovascular hypertensive rabbits after treatment with losartan.	2001 Mar	11243422
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 losartan on degree of mitral regurgitation quantified by echocardiography.	2001 Mar 1	11230841
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.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 18:46:55 GMT 2023` Edited by `admin` on `Sat Dec 16 18:46:55 GMT 2023`
Record UNII	A9DA3R9ZCK
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LOSARTAN HYDROCHLORIDE

Common Name

English

1H-IMIDAZOLE-5-METHANOL, 2-BUTYL-4-CHLORO-1-((2'-(2H-TETRAZOL-5-YL)(1,1'-BIPHENYL)-4-YL)METHYL)-, HYDROCHLORIDE

Systematic Name

English

1H-IMIDAZOLE-5-METHANOL, 2-BUTYL-4-CHLORO-1-((2'-(1H-TETRAZOL-5-YL)(1,1'-BIPHENYL)-4-YL)METHYL)-, HYDROCHLORIDE

Systematic Name

English

Code System Code Type Description

SMS_ID

100000125905

Created by admin on Sat Dec 16 18:46:55 GMT 2023 , Edited by admin on Sat Dec 16 18:46:55 GMT 2023

PRIMARY

CAS

343311-44-4

Created by admin on Sat Dec 16 18:46:55 GMT 2023 , Edited by admin on Sat Dec 16 18:46:55 GMT 2023

NON-SPECIFIC STOICHIOMETRY

FDA UNII

A9DA3R9ZCK

Created by admin on Sat Dec 16 18:46:55 GMT 2023 , Edited by admin on Sat Dec 16 18:46:55 GMT 2023

PRIMARY

PUBCHEM

18318845

Created by admin on Sat Dec 16 18:46:55 GMT 2023 , Edited by admin on Sat Dec 16 18:46:55 GMT 2023

PRIMARY

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LOSARTAN

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Amount:

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					JMS50MPO89

LOSARTAN

ACTIVE MOIETY

Amount:

Details

SMILES

InChI

DescriptionSources: https://www.drugs.com/monograph/cozaar.html

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Approved Use

Launch Date

Approved Use

Launch Date

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

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

C_max

T_1/2

F_unbound

Drug as perpetrator