Identification

Name
Glisoxepide
Accession Number
DB01289
Type
Small Molecule
Groups
Approved, Investigational
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 IDs
BAY B 4231 / FBB 4231 / RP 22410
International/Other Brands
Glucoben (Farmades) / Glysepin (Bayer) / Pro-Diaban (Bayer)
Categories
UNII
H7SC0I332I
CAS number
25046-79-1
Weight
Average: 449.524
Monoisotopic: 449.173289689
Chemical Formula
C20H27N5O5S
InChI Key
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

Pharmacology

Indication

For the treatment of diabetes mellitus type 2.

Structured Indications
Not Available
Pharmacodynamics

Glisoxepide 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 action

Glisoxepide 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.

TargetActionsOrganism
AATP-sensitive inward rectifier potassium channel 8
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not 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
Aluminium clofibrateAluminium clofibrate may increase the hypoglycemic activities of Glisoxepide.Experimental
ArotinololArotinolol may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
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, Investigational
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, Investigational
ClofibrateClofibrate may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
ClofibrideClofibride may increase the hypoglycemic activities of Glisoxepide.Experimental
CloranololCloranolol may increase the hypoglycemic activities of Glisoxepide.Experimental
ClorindioneGlisoxepide may increase the anticoagulant activities of Clorindione.Experimental
DicoumarolGlisoxepide may increase the anticoagulant activities of Dicoumarol.Approved
DiphenadioneGlisoxepide may increase the anticoagulant activities of Diphenadione.Experimental
DulaglutideDulaglutide may increase the hypoglycemic activities of Glisoxepide.Approved
EmpagliflozinEmpagliflozin may increase the hypoglycemic activities of Glisoxepide.Approved
EpanololEpanolol may increase the hypoglycemic activities of Glisoxepide.Experimental
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
Fenofibric acidFenofibric acid 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
LandiololLandiolol may increase the hypoglycemic activities of Glisoxepide.Investigational
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
MepindololMepindolol may increase the hypoglycemic activities of Glisoxepide.Experimental
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, Investigational
PhenprocoumonGlisoxepide may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
PindololPindolol may increase the hypoglycemic activities of Glisoxepide.Approved
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
RonifibrateRonifibrate may increase the hypoglycemic activities of Glisoxepide.Experimental
SaxagliptinSaxagliptin may increase the hypoglycemic activities of Glisoxepide.Approved
SimfibrateSimfibrate may increase the hypoglycemic activities of Glisoxepide.Experimental
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
TalinololTalinolol may increase the hypoglycemic activities of Glisoxepide.Investigational
TertatololTertatolol may increase the hypoglycemic activities of Glisoxepide.Experimental
TimololTimolol may increase the hypoglycemic activities of Glisoxepide.Approved
TioclomarolGlisoxepide may increase the anticoagulant activities of Tioclomarol.Experimental
TroglitazoneTroglitazone may increase the hypoglycemic activities of Glisoxepide.Investigational, 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 Interactions
Not Available

References

Synthesis Reference

U.S. Patent 3,668,215.

General References
Not Available
External Links
Human Metabolome Database
HMDB15406
PubChem Compound
32778
PubChem Substance
46508780
ChemSpider
30380
ChEBI
135731
ChEMBL
CHEMBL2106618
Therapeutic Targets Database
DAP000925
PharmGKB
PA164743233
ATC Codes
A10BB11 — Glisoxepide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus3

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)189 °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 RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

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 benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
Benzenesulfonyl compounds / 2-heteroaryl carboxamides / Sulfonylureas / Azepanes / Semicarbazides / Aminosulfonyl compounds / Heteroaromatic compounds / Isoxazoles / Organosulfonic acids and derivatives / Secondary carboxylic acid amides
show 7 more
Substituents
Benzenesulfonamide / Benzenesulfonyl group / 2-heteroaryl carboxamide / Azepane / Sulfonylurea / Azole / Isoxazole / Semicarbazide / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not 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...
Gene Name
KCNJ8
Uniprot ID
Q15842
Uniprot Name
ATP-sensitive inward rectifier potassium channel 8
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]

Drug created on June 28, 2007 09:58 / Updated on November 09, 2017 02:58