Azosemide

Identification

Name
Azosemide
Accession Number
DB08961
Type
Small Molecule
Groups
Investigational
Description

Azosemide is a loop diuretic used to treat hypertension, edema, and ascites.

Structure
Thumb
Synonyms
  • 2-chloro-5-(1H-tetrazol-5-yl)-N4-2-thenylsulfanilamide
  • 5-(4'-chloro-5'-sulfamoyl-2'-thenylaminophenyl)tetrazole
  • azosemida
  • azosémide
  • azosemidum
Categories
UNII
MR40VT1L8Z
CAS number
27589-33-9
Weight
Average: 370.838
Monoisotopic: 370.007342713
Chemical Formula
C12H11ClN6O2S2
InChI Key
HMEDEBAJARCKCT-UHFFFAOYSA-N
InChI
InChI=1S/C12H11ClN6O2S2/c13-9-5-10(15-6-7-2-1-3-22-7)8(12-16-18-19-17-12)4-11(9)23(14,20)21/h1-5,15H,6H2,(H2,14,20,21)(H,16,17,18,19)
IUPAC Name
2-chloro-5-(2H-1,2,3,4-tetrazol-5-yl)-4-[(thiophen-2-ylmethyl)amino]benzene-1-sulfonamide
SMILES
NS(=O)(=O)C1=C(Cl)C=C(NCC2=CC=CS2)C(=C1)C1=NNN=N1

Pharmacology

Indication
Not Available
Pharmacodynamics

Diuretic affects upon oral administration match those of furosemide. However, upon intravenous administration azosemide displays 5.5 to 8 times greater effect.

Mechanism of action

Exact mechanism of action is unclear. However, it acts primarily on the loop of Henle, in both the medullary and cortical segments of the thick ascending limb.

Absorption

Peak plasma concentrations are achieved in 3-4 hours when azosemide is administered to healthy humans in a fasting state. There is an absorption lag time of approximately 1 hour. Oral bioavailability estimated to be 20.4%

Volume of distribution

Poor affinity for human tissue. Small apparent post-pseudodistribution Vd of 0.262 l/kg.

Protein binding

> 95% 4% protein binding to 4% human serum albumin at azosemide concentrations of 10-100ug/ml, using equilibrium dialysis.

Metabolism

Considerable first pass metabolism which makes parentral administration more effective than oral administration. Eleven metabolites of azosemide were found in rats, but only azosemide and its glucuronide were detected in humans.

Route of elimination

Total body clearance 112ml/min. Renal clearance 41.6ml/min. Actively secreted in the renal proximal tubule of humans. This may or may not involve a nonspecific organic acid secretory pathway. There is thus a potential for disease states and other organic acids such as NSAIDs which affect the organic acid transport pathway to affect the efficacy of azosemide.

Half life

Terminal half life 2-3 hours.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe therapeutic efficacy of Azosemide can be decreased when used in combination with (4R)-limonene.
16-Bromoepiandrosterone16-Bromoepiandrosterone may increase the hypokalemic activities of Azosemide.
19-norandrostenedione19-norandrostenedione may increase the hypokalemic activities of Azosemide.
5-androstenedione5-androstenedione may increase the hypokalemic activities of Azosemide.
AbediterolAbediterol may increase the hypokalemic activities of Azosemide.
AcarboseThe therapeutic efficacy of Acarbose can be increased when used in combination with Azosemide.
AceclofenacThe therapeutic efficacy of Azosemide can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Azosemide can be decreased when used in combination with Acemetacin.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Azosemide.
AcetyldigitoxinThe risk or severity of adverse effects can be increased when Azosemide is combined with Acetyldigitoxin.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0041831
PubChem Compound
2273
PubChem Substance
347827814
ChemSpider
2186
ChEBI
31248
ChEMBL
CHEMBL1097235
Wikipedia
Azosemide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentCongestive Heart Failure (CHF)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0929 mg/mLALOGPS
logP2.36ALOGPS
logP2.38ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)7.38ChemAxon
pKa (Strongest Basic)-0.77ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area126.65 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity102.08 m3·mol-1ChemAxon
Polarizability34.56 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenyltetrazoles and derivatives. These are compounds containing a phenyltetrazole skeleton, which consists of a tetrazole bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Tetrazoles
Direct Parent
Phenyltetrazoles and derivatives
Alternative Parents
Aminobenzenesulfonamides / Benzenesulfonyl compounds / Phenylalkylamines / Aniline and substituted anilines / Secondary alkylarylamines / Chlorobenzenes / Organosulfonamides / Aryl chlorides / Thiophenes / Aminosulfonyl compounds
show 6 more
Substituents
Aminobenzenesulfonamide / Phenyltetrazole / Benzenesulfonamide / Benzenesulfonyl group / Aniline or substituted anilines / Phenylalkylamine / Chlorobenzene / Halobenzene / Secondary aliphatic/aromatic amine / Aralkylamine
show 24 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
sulfonamide, thiophenes, tetrazoles, monochlorobenzenes (CHEBI:31248)

Drug created on May 30, 2014 09:41 / Updated on October 01, 2018 14:44