Losartan chemical structure (angiotensin II receptor blocker), 2D skeletal formula, C22H23ClN6O

Losartan Chemical Structure

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1. Identification

Summary

Losartan is an angiotensin II receptor blocker (ARB) for hypertension, diabetic nephropathy in type 2 diabetes with proteinuria, and risk reduction of stroke in hypertensive patients with left ventricular hypertrophy.

Brand Names

Cozaar; numerous generics

Name

Losartan

Background

First-in-class ARB; marketed commonly as the potassium salt for oral tablets and fixed-dose combinations with hydrochlorothiazide.

Modality

Small molecule

Groups

Approved; prescription

Structure

Losartan Chemical Structure — ARB, 2D Skeletal Formula, C22H23ClN6O, CAS 114798-26-4
Losartan chemical structure (angiotensin II receptor blocker), 2D skeletal formula, C22H23ClN6O

Weight

~422.91 g/mol (free base)

Chemical Formula

C₂₂H₂₃ClN₆O (free base)

Synonyms

(2-butyl-4-chloro-1-{[2′-(2H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methanol; losartan free base; losartan potassium (salt form)

External IDs

CAS (base): 114798-26-4; PubChem CID: 3961; UNII (base): JMS50MPO89; ATC: C09CA01; KEGG: D08146

2. Pharmacology

Indication

Hypertension; diabetic nephropathy in T2DM with elevated urinary albumin; reduction of stroke risk in hypertensive patients with LVH.

Associated Conditions

Hypertension with compelling indications; proteinuric kidney disease; LVH.

Associated Therapies

Monotherapy or combined with thiazide diuretics; combinations with other antihypertensives per guidelines.

Contraindications & Blackbox Warnings

Boxed warning (pregnancy): drugs acting on the renin–angiotensin system can cause injury and death to the developing fetus. Contraindicated in pregnancy.

Pharmacodynamics

Selective antagonism of AT₁ receptors reduces vasoconstriction and aldosterone effects; active carboxylic acid metabolite EXP3174 contributes substantially to effect.

Mechanism of action

Competitive AT₁ receptor blockade; feedback increases plasma renin activity and angiotensin II, but receptor antagonism prevents downstream vasoconstriction and aldosterone release.

Absorption

Oral absorption with ~33% systemic bioavailability; peak tₘₐₓ ≈1 h for losartan and 3–4 h for EXP3174.

Volume of distribution

Approx. ~34 L for losartan; ~12 L for EXP3174.

Protein binding

High: ~98–99% (albumin-dominant).

Metabolism

Hepatic CYP2C9 and CYP3A4 form active EXP3174 and other metabolites.

Route of elimination

Renal and biliary/fecal elimination, mostly as metabolites.

Half-life

Losartan ~2 h; active metabolite ~6–9 h.

Clearance

Hepatic metabolism and biliary/renal routes; exposure increased in hepatic impairment.

Adverse Effects

Dizziness, upper respiratory infection, back pain; class risks include hyperkalemia, symptomatic hypotension, renal function changes, and rare angioedema.

Toxicity

Overdose management is supportive with monitoring of BP, renal function, and electrolytes.

Pathways

Renin–angiotensin–aldosterone system blockade at AT₁; downstream reduction in vasoconstriction and aldosterone-mediated sodium retention.

Pharmacogenomic Effects/ADRs

No required PGx; CYP2C9 variability may influence metabolite formation; monitor when strong enzyme modulators are present.

3. Interactions

Drug Interactions

Potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium → hyperkalemia risk.
Lithium → increased lithium exposure and toxicity risk.
NSAIDs → reduced antihypertensive effect; renal risk, especially with dehydration or CKD.
Aliskiren → avoid with diabetes; monitor if combined otherwise.
Dual RAAS blockade with ACE inhibitors or other ARBs → not recommended due to renal and hyperkalemia risk.

Food Interactions

Food has minimal effect on overall exposure; administer consistently.

4. Categories

ATC Codes

C09CA01 (ARB, plain)

Drug Categories

Angiotensin II receptor blocker; Antihypertensive; Small molecule

Chemical Taxonomy

Biphenyl tetrazole bioisostere of carboxylate; imidazole core; administered commonly as potassium salt

Affected organisms

Humans (therapeutic use)

5. Chemical Identifiers

UNII

JMS50MPO89 (losartan, base)

CAS number

114798-26-4 (losartan, base)

InChI Key

PSIFNNKUMBGKDQ-UHFFFAOYSA-N

InChI

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)

IUPAC Name

(2-butyl-4-chloro-1-{[2′-(2H-1,2,3,4-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl]methyl}-1H-imidazol-5-yl)methanol

SMILES

CCCCc1nc(Cl)c(CO)n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1

6. References

DailyMed — Losartan potassium tablets: PK (bioavailability ~33%, tₘₐₓ 1 h/3–4 h), distribution (~34 L/12 L), protein binding (~98–99%), mechanism, warnings. DailyMed+3DailyMed+3DailyMed+3
PubChem / Merck Index — identifiers (formula C₂₂H₂₃ClN₆O, MW ~422.91), IUPAC, InChI, InChIKey. Merck Index+1
precision.fda (UNII) — losartan base JMS50MPO89; losartan potassium 3ST302B24A. precisionFDA+1
ATC/KEGG — C09CA01 classification and cross-references. Genome
StatPearls — interaction themes (hyperkalemia with K⁺-raising agents), general clinical use overview. NCBI
MedicalNewsToday/GoodRx — practical interaction details (aliskiren in diabetes, lithium, NSAIDs, potassium). Medical News Today+1

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