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Identification
NameGlisoxepide
Accession NumberDB01289
TypeSmall Molecule
GroupsApproved
Description

Glisoxepide is one of the sulphonamide-derived oral antidiabetic drugs. It inhibits the uptake of bile acids into isolated rat hepatocytes. However it inhibits taurocholate uptake only in the absence of sodium ions. Glisoxepide uptake could be further inhibited by blockers of the hepatocellular monocarboxylate transporter, by the loop diuretic bumetanide, by 4,4’-diisothiocyano-2,2’-stilbenedisulfonate (DIDS) and by sulphate. These results are consistent with the transport of glisoxepide via the transport system for the unconjugated bile acid cholate.
(PMID:1618280, 9017793)

Structure
Thumb
Synonyms
BAY-b-4231
FBB-4231
Glisoxepide
RP-22410
External Identifiers Not Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
GlucobenFarmades
GlysepinBayer
Pro-DiabanBayer
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIH7SC0I332I
CAS number25046-79-1
WeightAverage: 449.524
Monoisotopic: 449.173289689
Chemical FormulaC20H27N5O5S
InChI KeyInChIKey=ZKUDBRCEOBOWLF-UHFFFAOYSA-N
InChI
InChI=1S/C20H27N5O5S/c1-15-14-18(23-30-15)19(26)21-11-10-16-6-8-17(9-7-16)31(28,29)24-20(27)22-25-12-4-2-3-5-13-25/h6-9,14H,2-5,10-13H2,1H3,(H,21,26)(H2,22,24,27)
IUPAC Name
N-{2-[4-({[(azepan-1-yl)carbamoyl]amino}sulfonyl)phenyl]ethyl}-5-methyl-1,2-oxazole-3-carboxamide
SMILES
CC1=CC(=NO1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN1CCCCCC1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzenesulfonamides
Direct ParentBenzenesulfonamides
Alternative Parents
Substituents
  • Benzenesulfonamide
  • Phenethylamine
  • Sulfonylurea
  • Azepane
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Semicarbazide
  • Oxazole
  • Isoxazole
  • Azole
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of diabetes mellitus type 2.
PharmacodynamicsGlisoxepide is a sulfonylurea agent. It stimulates beta cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall it potentiates insulin release and improves insulin dynamics.
Mechanism of actionGlisoxepide is a hypoglycemic sulphonylurea agent. The sulphonylureas are a family of drugs based on a common sulphonylurea core. These drugs act via augmentation of secretion of insulin from pancreatic beta-cells. Sulphonylureas may also cause a reduction in serum glucagon and potentiate the action of insulin at the extrapancreatic tissues. Glisoxepide functions as a non-selective K(ATP) channel blocker. It is thought to stimulate insulin secretion by closing the ATP-sensitive K(+) (K(ATP)) channels (Kir6.2/SUR1 complex, KATP channels) in pancreatic beta-cells. This inhibits a tonic, hyperpolarizing efflux of potassium, thus causing the electric potential over the membrane to become more positive. This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9787
Blood Brain Barrier+0.741
Caco-2 permeable-0.6772
P-glycoprotein substrateSubstrate0.594
P-glycoprotein inhibitor INon-inhibitor0.7578
P-glycoprotein inhibitor IINon-inhibitor0.9445
Renal organic cation transporterNon-inhibitor0.8195
CYP450 2C9 substrateSubstrate0.5621
CYP450 2D6 substrateNon-substrate0.8474
CYP450 3A4 substrateNon-substrate0.6478
CYP450 1A2 substrateNon-inhibitor0.9188
CYP450 2C9 inhibitorNon-inhibitor0.6091
CYP450 2D6 inhibitorNon-inhibitor0.848
CYP450 2C19 inhibitorNon-inhibitor0.7913
CYP450 3A4 inhibitorNon-inhibitor0.6763
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7438
Ames testNon AMES toxic0.7018
CarcinogenicityNon-carcinogens0.7506
BiodegradationReady biodegradable0.5877
Rat acute toxicity1.6845 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7225
hERG inhibition (predictor II)Non-inhibitor0.6458
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point189 °CPhysProp, U.S. Patent 3,668,215.
Predicted Properties
PropertyValueSource
Water Solubility0.103 mg/mLALOGPS
logP1.57ALOGPS
logP1.44ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)4.07ChemAxon
pKa (Strongest Basic)1.59ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area133.64 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity115.86 m3·mol-1ChemAxon
Polarizability46.83 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

U.S. Patent 3,668,215.

General ReferencesNot Available
External Links
ATC CodesA10BB11
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Inward rectifier potassium channel activity
Specific Function:
This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward...
Gene Name:
KCNJ8
Uniprot ID:
Q15842
Molecular Weight:
47967.455 Da
References
  1. Szewczyk A, Wojcik G, Lobanov NA, Nalecz MJ: The mitochondrial sulfonylurea receptor: identification and characterization. Biochem Biophys Res Commun. 1997 Jan 23;230(3):611-5. [PubMed:9015372 ]
  2. Sato T, Costa AD, Saito T, Ogura T, Ishida H, Garlid KD, Nakaya H: Bepridil, an antiarrhythmic drug, opens mitochondrial KATP channels, blocks sarcolemmal KATP channels, and confers cardioprotection. J Pharmacol Exp Ther. 2006 Jan;316(1):182-8. Epub 2005 Sep 20. [PubMed:16174795 ]
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Drug created on June 28, 2007 09:58 / Updated on January 15, 2016 17:38