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Identification
Name Glisoxepide
Accession Number DB01289
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories Not Available
CAS number 25046-79-1
Weight Average: 449.524
Monoisotopic: 449.173289689
Chemical Formula C20H27N5O5S
InChI Key InChIKey=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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Sulfonylureas
Substructures
  • Sulfonylureas
  • Amino Ketones
  • Sulfonyls
  • Benzene and Derivatives
  • Isoxazoles
  • Carboxylic Acids and Derivatives
  • Benzenesulfonamides
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Oxazoles
  • Sulfonamides
  • Semicarbazides
  • Hydrazine Derivatives
  • Imines
Pharmacology
Indication For the treatment of diabetes mellitus type 2.
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.
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
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 189 °C PhysProp
Predicted Properties
Property Value Source
water solubility 1.03e-01 g/l ALOGPS
logP 1.57 ALOGPS
logP 1.44 ChemAxon
logS -3.6 ALOGPS
pKa (strongest acidic) 4.07 ChemAxon
pKa (strongest basic) 1.59 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 133.64 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 115.86 ChemAxon
polarizability 46.83 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PubChem Compound 32778 Link_out
PubChem Substance 46508780 Link_out
ChemSpider 30380 Link_out
Therapeutic Targets Database DAP000925 Link_out
PharmGKB PA164743233 Link_out
ATC Codes
  • A10BB11
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Acebutolol The beta-blocker, acebutolol, may decrease symptoms of hypoglycemia.
Acetylsalicylic acid Acetylsalicylic acid increases the effect of the sulfonylurea, glisoxepide.
Atenolol The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
Bisoprolol The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
Carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Chloramphenicol Chloramphenicol may increase the effect of sulfonylurea, glisoxepide.
Clofibrate Clofibrate may increase the effect of sulfonylurea, glisoxepide.
Esmolol The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
Labetalol The beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
Metoprolol The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
Nadolol The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.
Oxprenolol The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.
Phenylbutazone Phenylbutazone increases the effect of the hypoglycemic agent
Pindolol The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
Propranolol The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
Rifampin Rifampin may decrease the effect of sulfonylurea, glisoxepide.
Timolol The beta-blocker, timolol, may decrease symptoms of hypoglycemia.
Food Interactions Not Available
Targets

1. ATP-sensitive inward rectifier potassium channel 8

Pharmacological action: yes
Actions: inhibitor

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 rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium (By similarity)

Organism class: human
UniProt ID: Q15842 Link_out
Gene: KCNJ8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Drug created on June 28, 2007 09:58 / Updated on February 08, 2013 16:20