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Identification
NamePolythiazide
Accession NumberDB01324
TypeSmall Molecule
GroupsApproved
Description

A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p826)

Structure
Thumb
Synonyms
SynonymLanguageCode
ReneseNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number346-18-9
WeightAverage: 439.882
Monoisotopic: 438.970880311
Chemical FormulaC11H13ClF3N3O4S3
InChI KeyCYLWJCABXYDINA-UHFFFAOYSA-N
InChI
InChI=1S/C11H13ClF3N3O4S3/c1-18-10(4-23-5-11(13,14)15)17-7-2-6(12)8(24(16,19)20)3-9(7)25(18,21)22/h2-3,10,17H,4-5H2,1H3,(H2,16,19,20)
IUPAC Name
6-chloro-2-methyl-1,1-dioxo-3-{[(2,2,2-trifluoroethyl)sulfanyl]methyl}-3,4-dihydro-2H-1λ⁶,2,4-benzothiadiazine-7-sulfonamide
SMILES
CN1C(CSCC(F)(F)F)NC2=CC(Cl)=C(C=C2S1(=O)=O)S(N)(=O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzothiadiazines. These are organic compounds containing a benzene fused to a thiadiazine ring (a six-member ring with two nitrogen atoms and a sulfur atom).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassThiadiazines
Sub ClassBenzothiadiazines
Direct ParentBenzothiadiazines
Alternative Parents
Substituents
  • Benzothiadiazine
  • Benzenesulfonamide
  • Secondary aliphatic/aromatic amine
  • Chlorobenzene
  • Benzenoid
  • Aryl halide
  • Aryl chloride
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Azacycle
  • Dialkylthioether
  • Sulfenyl compound
  • Thioether
  • Secondary amine
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organonitrogen compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationPolythiazide is a thiazide diuretic used to decrease edema and decrease blood pressure.
PharmacodynamicsAs a thiazide diuretic, Polythiazide inhibits the sodium-chloride symporter which decreases solute reabsorption leading to a retention of water in the urine, as water normally follows solutes. More frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure
Mechanism of actionAs a diuretic, polythiazide inhibits active chloride reabsorption at the early distal tubule via the thiazide-sensitive Na-Cl cotransporter (TSC), resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like polythiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of polythiazide may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9884
Blood Brain Barrier-0.5727
Caco-2 permeable-0.6601
P-glycoprotein substrateSubstrate0.6985
P-glycoprotein inhibitor INon-inhibitor0.7714
P-glycoprotein inhibitor IINon-inhibitor0.8974
Renal organic cation transporterNon-inhibitor0.776
CYP450 2C9 substrateNon-substrate0.6019
CYP450 2D6 substrateNon-substrate0.8108
CYP450 3A4 substrateNon-substrate0.5091
CYP450 1A2 substrateNon-inhibitor0.7786
CYP450 2C9 substrateNon-inhibitor0.5713
CYP450 2D6 substrateNon-inhibitor0.8479
CYP450 2C19 substrateNon-inhibitor0.7738
CYP450 3A4 substrateInhibitor0.6198
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6625
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8224
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.3534 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8884
hERG inhibition (predictor II)Non-inhibitor0.8734
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point214 °CPhysProp
logP1.90SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.264 mg/mLALOGPS
logP2.13ALOGPS
logP1.1ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)9.31ChemAxon
pKa (Strongest Basic)-3.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area109.57 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity90.52 m3·mol-1ChemAxon
Polarizability37.56 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesC03AA05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Solute carrier family 12 member 3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 12 member 3 P55017 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Monroy A, Plata C, Hebert SC, Gamba G: Characterization of the thiazide-sensitive Na(+)-Cl(-) cotransporter: a new model for ions and diuretics interaction. Am J Physiol Renal Physiol. 2000 Jul;279(1):F161-9. Pubmed
  3. Frindt G, McNair T, Dahlmann A, Jacobs-Palmer E, Palmer LG: Epithelial Na channels and short-term renal response to salt deprivation. Am J Physiol Renal Physiol. 2002 Oct;283(4):F717-26. Pubmed

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Drug created on June 30, 2007 11:21 / Updated on September 16, 2013 17:14