You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
GlucobenFarmades
GlysepinBayer
Pro-DiabanBayer
Brand mixturesNot Available
CategoriesNot Available
CAS number25046-79-1
WeightAverage: 449.524
Monoisotopic: 449.173289689
Chemical FormulaC20H27N5O5S
InChI KeyZKUDBRCEOBOWLF-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentBenzenesulfonamides
Alternative parentsPhenethylamines; Sulfonylureas; Azepanes; Semicarbazides; Isoxazoles; Sulfonamides; Sulfonyls; Secondary Carboxylic Acid Amides; Enolates; Carboxylic Acids; Polyamines
Substituentsazepane; sulfonylurea; sulfonamide; azole; isoxazole; sulfonic acid derivative; sulfonyl; semicarbazide; carboxamide group; secondary carboxylic acid amide; enolate; polyamine; carboxylic acid derivative; carboxylic acid; amine; hydrazine derivative; organonitrogen compound
Classification descriptionThis compound belongs to the benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
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
Property Value Probability
Human Intestinal Absorption + 0.9787
Blood Brain Barrier + 0.741
Caco-2 permeable - 0.6772
P-glycoprotein substrate Substrate 0.594
P-glycoprotein inhibitor I Non-inhibitor 0.7578
P-glycoprotein inhibitor II Non-inhibitor 0.9445
Renal organic cation transporter Non-inhibitor 0.8195
CYP450 2C9 substrate Substrate 0.5621
CYP450 2D6 substrate Non-substrate 0.8474
CYP450 3A4 substrate Non-substrate 0.6478
CYP450 1A2 substrate Non-inhibitor 0.9188
CYP450 2C9 substrate Non-inhibitor 0.6091
CYP450 2D6 substrate Non-inhibitor 0.848
CYP450 2C19 substrate Non-inhibitor 0.7913
CYP450 3A4 substrate Non-inhibitor 0.6763
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7438
Ames test Non AMES toxic 0.7018
Carcinogenicity Non-carcinogens 0.7506
Biodegradation Ready biodegradable 0.5877
Rat acute toxicity 1.6845 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7225
hERG inhibition (predictor II) Non-inhibitor 0.6458
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 solubility1.03e-01 g/lALOGPS
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 area133.64ChemAxon
rotatable bond count6ChemAxon
refractivity115.86ChemAxon
polarizability46.83ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

U.S. Patent 3,668,215.

General ReferenceNot Available
External Links
ResourceLink
PubChem Compound32778
PubChem Substance46508780
ChemSpider30380
Therapeutic Targets DatabaseDAP000925
PharmGKBPA164743233
ATC CodesA10BB11
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcebutololThe beta-blocker, acebutolol, may decrease symptoms of hypoglycemia.
Acetylsalicylic acidAcetylsalicylic acid increases the effect of the sulfonylurea, glisoxepide.
AtenololThe beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
BisoprololThe beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
CarvedilolThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
ChloramphenicolChloramphenicol may increase the effect of sulfonylurea, glisoxepide.
ClofibrateClofibrate may increase the effect of sulfonylurea, glisoxepide.
EsmololThe beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
LabetalolThe beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
MetoprololThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
NadololThe beta-blocker, nadolol, may decrease symptoms of hypoglycemia.
OxprenololThe beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.
PhenylbutazonePhenylbutazone increases the effect of the hypoglycemic agent
PindololThe beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
PropranololThe beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
RifampicinRifampin may decrease the effect of sulfonylurea, glisoxepide.
TimololThe beta-blocker, timolol, may decrease symptoms of hypoglycemia.
Food InteractionsNot Available

Targets

1. ATP-sensitive inward rectifier potassium channel 8

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
ATP-sensitive inward rectifier potassium channel 8 Q15842 Details

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
  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

Comments
comments powered by Disqus
Drug created on June 28, 2007 09:58 / Updated on April 25, 2014 11:53