7-chloro-2-methyl-3-(2-methylphenyl)-4-oxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide

• ChemBase ID: 406
• Molecular Formular: C16H16ClN3O3S
• Molecular Mass: 365.83454
• Monoisotopic Mass: 365.06009007
• SMILES: Clc1cc2NC(N(C(=O)c2cc1S(=O)(=O)N)c1c(cccc1)C)C
• Canonical SMILES: CC1Nc2cc(Cl)c(cc2C(=O)N1c1ccccc1C)S(=O)(=O)N
• InChI: InChI=1S/C16H16ClN3O3S/c1-9-5-3-4-6-14(9)20-10(2)19-13-8-12(17)15(24(18,22)23)7-11(13)16(20)21/h3-8,10,19H,1-2H3,(H2,18,22,23)
• InChIKey: AQCHWTWZEMGIFD-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 7-chloro-2-methyl-3-(2-methylphenyl)-4-oxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide
• IUPAC Traditional name: metolazone (product); metolazone
• Brand Name: Diulo; Metalazone; Metalozone; Metenix; Microx; Mykrox; Oldren; Xuret; Zaroxolyn
• Synonyms: Metolazona [INN-Spanish]; Metolazonum [INN-Latin]; Metolazone; Metolazone; 7-Chloro-1,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-6-quinazolinesulfonamide; Mykrox; Zaroxolyn; Diulo; Metolazone(Zaroxolyn); 7-Chloro-2-methyl-4-oxo-3-(o-tolyl)-1,2,3,4-tetrahydroquinazoline-6-sulfonamide; 2-Methyl-3-(o-tolyl)-6-sulfamyl-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone; Metenix; Metozalone; Normelan; Oldren; SR 720-22; Xuret

Database IDs

• CAS Number: 17560-51-9
• EC Number: 241-539-3
• MDL Number: MFCD00069304
• PubChem SID: 24724532; 46509058; 160963869
• PubChem CID: 4170

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.535759
• H Acceptors: 4
• H Donor: 2
• LogD (pH = 5.5): 2.943545
• LogD (pH = 7.4): 2.940775
• Log P: 2.9435806
• Molar Refractivity: 94.5879 cm^3
• Polarizability: 36.030464 Å^3
• Polar Surface Area: 92.5 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.21
• LOG S: -3.95
• Solubility (Water): 4.07e-02 g/l

PROPERTIES

Physical Property

• Solubility: 60.3 mg/L; Butanol; DMSO: >5 mg/mL; Ethanol
• Apperance: Crystalline Solid; white solid
• Melting Point: 248-250°C; 252-254°C (dec.)
• Hydrophobicity(logP): 2.5

Safety Information

• Storage Condition: -20°C; -20°C Freezer; Room Temperature (15-30°C)
• RTECS: VA1700000
• German water hazard class: 2
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Pharmacology Properties

• Gene Information: human ... SLC12A1(6557)

Product Information

• Purity: ≥98% (HPLC); 95+%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C16H16ClN3O3S

DETAILS

MP Biomedicals - 02153617

Diuretic; anti-hypertensive

DrugBank - DB00524

• Drug Groups: approved
• Description: A quinazoline-sulfonamide that is considered a thiazide-like diuretic which is long-acting so useful in chronic renal failure. It also tends to lower blood pressure and increase potassium loss. [PubChem]
• Indication: For the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class.
• Pharmacology: 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.
• Toxicity: Symptoms of overdose include difficulty breathing, dizziness, dizziness on standing up, drowsiness, fainting, irritation of the stomach and intestines, and lethargy leading to coma.
• Affected Organisms: Humans and other mammals
• Biotransformation: Not substantially metabolized. 70-95% is excreted unchanged in urine via glomerular filtration and active tubular secretion. Undergoes enterohepatic recycling.
• Absorption: Peak blood levels are obtained within 2 to 4 hours of oral administration. The rate and extent of absorption are formulation dependent.
• Half Life: Approximately 14 hours.
• Protein Binding: 50-70% bound to erythrocytes, up to 33% bound to plasma proteins, 2-5% of the drug in circulation is unbound
• Elimination: Most of the drug is excreted in the unconverted form in the urine.
• References: Rosenberg J, Gustafsson F, Galatius S, Hildebrandt PR: Combination therapy with metolazone and loop diuretics in outpatients with refractory heart failure: an observational study and review of the literature. Cardiovasc Drugs Ther. 2005 Aug;19(4):301-6. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1610

Research Area: Cardiovascular Disease
Biological Activity:
Metolazone(Zaroxolyn) is primarily used to treat congestive heart failure and high blood pressure. Metolazone indirectly decreases the amount of water reabsorbed into the bloodstream by the kidney, which results in the decreases of blood volume and the increases of urine volume. Metolazone and the other thiazide diuretics inhibit the function of the sodium-chloride symporter and prevent sodium and chloride, water as well, from leaving the lumen to enter the tubule cell. [1]

Sigma Aldrich - M1195

Biochem/physiol Actions
Inhibitor of thiazide-sensitive Na+-Cl- cotransporter; antihypertensive; moderate "loop" diuretic.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. M1195.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - M338750

A diruetic. An antihypertensive.

REFERENCES

• Rosenberg J, Gustafsson F, Galatius S, Hildebrandt PR: Combination therapy with metolazone and loop diuretics in outpatients with refractory heart failure: an observational study and review of the literature. Cardiovasc Drugs Ther. 2005 Aug;19(4):301-6. Pubmed
• http://en.wikipedia.org/wiki/Metolazone
• Curry, C.L., et al.: Clin. Ther., 9, 47 (1986)
• Kiyingi, A., et al.: Lancet, 335, 29 (1990)