Basic information
- CAS
17560-51-9- Standard SMILES
Cc1ccccc1N1C(=O)c2cc(S(N)(=O)=O)c(Cl)cc2NC1C- InChIKey
AQCHWTWZEMGIFD-UHFFFAOYSA-N- Molecular formula
- C16H16ClN3O3S
- Average molar mass
- 365.8 g/mol
- Monoisotopic mass
- 365.0600902
Overview
Metolazone is a quinazoline that consists of 1,2,3,4-tetrahydroquinazolin-4-one bearing additional methyl, 2-tolyl, sulfamyl and chloro substituents at positions 2, 3, 6 and 7 respectively. A quinazoline diuretic, with properties similar to thiazide diuretics. It has a role as a diuretic, an antihypertensive agent and an ion transport inhibitor. It is a sulfonamide, an organochlorine compound and a member of quinazolines.
Names & identifiers
- Preferred name
- Metolazone
- IUPAC
- 7-chloro-2-methyl-3-(2-methylphenyl)-4-oxo-1,2-dihydroquinazoline-6-sulfonamide
- English name
- metolazone
- Molecular formula
- C16H16ClN3O3S
- Molecular weight
- 365.83
Names & synonyms
metolazone17560-51-9ZaroxolynDiuloMykroxOldrenMetenixMetalozoneMetolazonaMetolazonummetozaloneNormelan
Show more names
XuretSR 720-227-Chloro-1,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-6-quinazolinesulfonamideSR-720-22Metazoline6-Quinazolinesulfonamide, 7-chloro-1,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-DTXSID60451677-Chloro-1,2,3,4-tetrahydro-2-methyl-4-oxo-3-o-tolyl-6-quinazolinesulfonamide
Database identifiers
- CAS
17560-51-9、56436-31-8、56436-32-9- PubChem CID
- 4170
- DTXSID
DTXSID6045167- ChEMBL
CHEMBL878- ChEBI
CHEBI:64354- UNII
- NM7V2Y3G0U、NN9U607695、TZ7V40X7VX
- EC Number
- 241-539-3
- Nikkaji
- J3.450I
Properties
Computed structural properties
- XLogP
- 4.1
- Topological polar surface area
- 101 Ų
- Hydrogen bond donors
- 2
- Hydrogen bond acceptors
- 5
- Rotatable bonds
- 2
- Heavy atoms
- 24
- Formal charge
- 0
- Complexity
- 594
Experimental & physicochemical properties
LogP
2.5
1.8
OdorODORLESS
TasteTASTELESS
Color/FormCRYSTALS FROM ETHANOL
Solubility
INSOL IN WATER & ALCOHOL
4.07e-02 g/L
Human Drugs
Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents; Thiazide Diuretics
FDA approved drugs -> Active ingredient
FDA approved drugs -> Active ingredient
Pharmaceuticals
Melting Point
253-259 °C
256 °C
Physical DescriptionSolid
Stability/Shelf LifeLIGHT-SENSITIVE
Dissociation ConstantsPKA: 9.72
Safety & regulation
Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.
GHS classification
GHS Classification
Warning
H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]
P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)
The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.
Hazard information
Hazard Classes and CategoriesSkin Irrit. 2 (100%)
Toxicology
Interactions
...METOLAZONE...CHEMICALLY & PHARMACOLOGICALLY RELATED TO THIAZIDE DIURETICS & ELEVATE SERUM URATE LEVELS. ...MAY...INTERACT WITH PROBENECID.
USE OF THIAZIDE DIURETIC MAY IMPAIR CONTROL OF DIABETES IN PT TREATED...WITH ORAL HYPOGLYCEMIC AGENTS OR INSULIN, BUT ONLY TO LIMITED EXTENT. /THIAZIDE DIURETICS/
METOLAZONE...STRUCTURALLY RELATED TO THIAZIDE DIURETICS, CAN CAUSE HYPOKALEMIA, & MAY BE EXPECTED TO INTERACT WITH CARDIAC GLYCOSIDES.
THIAZIDES ENHANCE ANTIHYPERTENSIVE ACTION OF GUANETHIDINE... /THIAZIDE DIURETICS/
For more Interactions (Complete) data for METOLAZONE (6 total), please visit the HSDB record page.
Adverse Effects
Hyperuricemia is a common adverse effect due to competitive inhibition of uric acid secretion and a decrease in extracellular fluid from diuretic effects. Other fluid and electrolyte imbalances may occur, especially hyponatremia, hypokalemia, and hypomagnesemia. Any electrolyte imbalances must be corrected before starting treatment. Metolazone may impair glucose tolerance, causing hyperglycemia and glycosuria. Diabetic patients should monitor their blood and urine glucose levels while on this therapy.
Chemistry & industry
Pharmacology
ATC Code
C - Cardiovascular system
QC - Cardiovascular system
Protein Binding50-70% bound to erythrocytes, up to 33% bound to plasma proteins, 2-5% of the drug in circulation is unbound
Pharmacodynamics
Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies.
Mechanism of Action
The actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Metolazone does not inhibit carbonic anhydrase. The antihypertensive mechanism of action of metolazone is not fully understood but is presumed to be related to its saluretic and diuretic properties.
IT ACTS PRIMARILY TO INHIBIT SODIUM REABSORPTION AT CORTICAL DILUTING SITE & IN PROXIMAL CONVOLUTED TUBULE. SODIUM & CHLORIDE IONS ARE EXCRETED IN APPROX EQUAL AMT; INCR POTASSIUM EXCRETION MAY ALSO OCCUR. DIURETIC POTENCY APPROXIMATES THAT OF THIAZIDES.
Biological Half-Life
Approximately 14 hours.
LONG T/2 VALUE...IN DOGS IS RELATED TO TRANSPORT MECHANISM IN BLOOD & PARTITION BETWEEN FORMED ELEMENTS & SERUM PROTEINS.
...METOLAZONE IS EXCRETED BY GLOMERULAR FILTRATION & TUBULAR SECRETION IN DOGS, ALTHOUGH DRUG:CREATININE CLEARANCE RATIO IS LOWER THAN FOR MOST OTHER DIURETICS. T/2 IN DOGS OF 5-6 HR IS INFLUENCED BY EXTENSIVE BINDING TO ERYTHROCYTES & PLASMA PROTEINS, & POSSIBLY TO TISSUE PROTEINS.
Metabolism/Metabolites
Related reactions
1 records
Compound notes
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