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Identification
NameGlisoxepide
Accession NumberDB01289
TypeSmall Molecule
GroupsApproved
DescriptionGlisoxepide 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
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not 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 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
Pharmacology
IndicationFor the treatment of diabetes mellitus type 2.
Structured Indications Not Available
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.
TargetKindPharmacological actionActionsOrganismUniProt ID
ATP-sensitive inward rectifier potassium channel 8Proteinyes
inhibitor
HumanQ15842 details
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
Interactions
Drug Interactions
DrugInteractionDrug group
AcebutololAcebutolol may increase the hypoglycemic activities of Glisoxepide.Approved
AcenocoumarolGlisoxepide may increase the anticoagulant activities of Acenocoumarol.Approved
AlbiglutideAlbiglutide may increase the hypoglycemic activities of Glisoxepide.Approved
AlogliptinAlogliptin may increase the hypoglycemic activities of Glisoxepide.Approved
AlprenololAlprenolol may increase the hypoglycemic activities of Glisoxepide.Approved, Withdrawn
Aop200704Aop200704 may increase the hypoglycemic activities of Glisoxepide.Investigational
ArotinololArotinolol may increase the hypoglycemic activities of Glisoxepide.Approved
AtenololAtenolol may increase the hypoglycemic activities of Glisoxepide.Approved
AtorvastatinAtorvastatin may increase the hypoglycemic activities of Glisoxepide.Approved
BefunololBefunolol may increase the hypoglycemic activities of Glisoxepide.Experimental
BetaxololBetaxolol may increase the hypoglycemic activities of Glisoxepide.Approved
BevantololBevantolol may increase the hypoglycemic activities of Glisoxepide.Approved
BezafibrateBezafibrate may increase the hypoglycemic activities of Glisoxepide.Approved
BisoprololBisoprolol may increase the hypoglycemic activities of Glisoxepide.Approved
BopindololBopindolol may increase the hypoglycemic activities of Glisoxepide.Approved
BucindololBucindolol may increase the hypoglycemic activities of Glisoxepide.Investigational
BufuralolBufuralol may increase the hypoglycemic activities of Glisoxepide.Experimental, Investigational
BupranololBupranolol may increase the hypoglycemic activities of Glisoxepide.Approved
CanagliflozinCanagliflozin may increase the hypoglycemic activities of Glisoxepide.Approved
CarbocisteineThe risk or severity of adverse effects can be increased when Glisoxepide is combined with Carbocisteine.Approved
CarteololCarteolol may increase the hypoglycemic activities of Glisoxepide.Approved
CarvedilolCarvedilol may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
CeliprololCeliprolol may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
ChloramphenicolThe metabolism of Glisoxepide can be decreased when combined with Chloramphenicol.Approved, Vet Approved
CimetidineThe serum concentration of Glisoxepide can be increased when it is combined with Cimetidine.Approved
CiprofibrateCiprofibrate may increase the hypoglycemic activities of Glisoxepide.Approved
ClofibrateClofibrate may increase the hypoglycemic activities of Glisoxepide.Approved
DicoumarolGlisoxepide may increase the anticoagulant activities of Dicoumarol.Approved
DulaglutideDulaglutide may increase the hypoglycemic activities of Glisoxepide.Approved
EmpagliflozinEmpagliflozin may increase the hypoglycemic activities of Glisoxepide.Approved
EsmololEsmolol may increase the hypoglycemic activities of Glisoxepide.Approved
EthanolThe risk or severity of adverse effects can be increased when Glisoxepide is combined with Ethanol.Approved
Ethyl biscoumacetateGlisoxepide may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
EtofibrateEtofibrate may increase the hypoglycemic activities of Glisoxepide.Approved
ExenatideExenatide may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
FenofibrateFenofibrate may increase the hypoglycemic activities of Glisoxepide.Approved
FluconazoleThe serum concentration of Glisoxepide can be increased when it is combined with Fluconazole.Approved
FluindioneGlisoxepide may increase the anticoagulant activities of Fluindione.Investigational
GemfibrozilGemfibrozil may increase the hypoglycemic activities of Glisoxepide.Approved
IndenololIndenolol may increase the hypoglycemic activities of Glisoxepide.Withdrawn
LabetalolLabetalol may increase the hypoglycemic activities of Glisoxepide.Approved
LevobunololLevobunolol may increase the hypoglycemic activities of Glisoxepide.Approved
LinagliptinLinagliptin may increase the hypoglycemic activities of Glisoxepide.Approved
LiraglutideLiraglutide may increase the hypoglycemic activities of Glisoxepide.Approved
MetipranololMetipranolol may increase the hypoglycemic activities of Glisoxepide.Approved
MetoprololMetoprolol may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
MetreleptinMetreleptin may increase the hypoglycemic activities of Glisoxepide.Approved
MiconazoleMiconazole may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational, Vet Approved
NadololNadolol may increase the hypoglycemic activities of Glisoxepide.Approved
OxprenololOxprenolol may increase the hypoglycemic activities of Glisoxepide.Approved
PenbutololPenbutolol may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
PhenindioneGlisoxepide may increase the anticoagulant activities of Phenindione.Approved
PhenprocoumonGlisoxepide may increase the anticoagulant activities of Phenprocoumon.Approved
PindololPindolol may increase the hypoglycemic activities of Glisoxepide.Approved
PioglitazonePioglitazone may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
PractololPractolol may increase the hypoglycemic activities of Glisoxepide.Approved
ProbenecidThe protein binding of Glisoxepide can be decreased when combined with Probenecid.Approved
PropranololPropranolol may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
RanitidineThe serum concentration of Glisoxepide can be increased when it is combined with Ranitidine.Approved
RifampicinThe serum concentration of Glisoxepide can be decreased when it is combined with Rifampicin.Approved
RosiglitazoneRosiglitazone may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
SaxagliptinSaxagliptin may increase the hypoglycemic activities of Glisoxepide.Approved
SitagliptinSitagliptin may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
SotalolSotalol may increase the hypoglycemic activities of Glisoxepide.Approved
SulfadiazineSulfadiazine may increase the hypoglycemic activities of Glisoxepide.Approved, Vet Approved
SulfamethoxazoleSulfamethoxazole may increase the hypoglycemic activities of Glisoxepide.Approved
SulfisoxazoleSulfisoxazole may increase the hypoglycemic activities of Glisoxepide.Approved, Vet Approved
TimololTimolol may increase the hypoglycemic activities of Glisoxepide.Approved
TroglitazoneTroglitazone may increase the hypoglycemic activities of Glisoxepide.Withdrawn
VildagliptinVildagliptin may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
VoriconazoleThe serum concentration of Glisoxepide can be increased when it is combined with Voriconazole.Approved, Investigational
WarfarinGlisoxepide may increase the anticoagulant activities of Warfarin.Approved
Food InteractionsNot 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
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
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
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

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 August 17, 2016 12:23