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Identification
NameGlycodiazine
Accession NumberDB01382
TypeSmall Molecule
GroupsApproved
Description

Glycodiazine is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin. The mechanism of action of glycodiazine in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Glycodiazine likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. This increase in intracellular calcium ion concentration induces the secretion of insulin. It is used for the concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.

Structure
Thumb
Synonyms
SynonymLanguageCode
GlidiazineNot AvailableNot Available
GlymidineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
GlycanolBayer
GlyconormalBayer
GondafonSchering
LycanolBayer
RedulBayer
Brand mixturesNot Available
CategoriesNot Available
CAS number339-44-6
WeightAverage: 309.341
Monoisotopic: 309.078326673
Chemical FormulaC13H15N3O4S
InChI KeyQFWPJPIVLCBXFJ-UHFFFAOYSA-N
InChI
InChI=1S/C13H15N3O4S/c1-19-7-8-20-11-9-14-13(15-10-11)16-21(17,18)12-5-3-2-4-6-12/h2-6,9-10H,7-8H2,1H3,(H,14,15,16)
IUPAC Name
N-[5-(2-methoxyethoxy)pyrimidin-2-yl]benzenesulfonamide
SMILES
COCCOC1=CN=C(NS(=O)(=O)C2=CC=CC=C2)N=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentBenzenesulfonamides
Alternative parentsAlkyl Aryl Ethers; Pyrimidines and Pyrimidine Derivatives; Sulfonamides; Sulfonyls; Polyamines
Substituentsalkyl aryl ether; pyrimidine; sulfonamide; sulfonic acid derivative; sulfonyl; ether; polyamine; amine; 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
IndicationGlycodiazine is used concomitantly with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.
PharmacodynamicsGlycodiazine is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin.
Mechanism of actionThe mechanism of action of glycodiazine in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Glycodiazine likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.
AbsorptionRapidly and completely absorbed following oral administration.
Volume of distributionNot Available
Protein binding90% bound to plasma proteins.
Metabolism
Route of eliminationNot Available
Half life4 hours.
ClearanceNot Available
ToxicitySevere hypoglycemic reactions with coma, seizure, or other neurological impairment.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9892
Blood Brain Barrier + 0.7927
Caco-2 permeable - 0.6157
P-glycoprotein substrate Non-substrate 0.6453
P-glycoprotein inhibitor I Non-inhibitor 0.5185
P-glycoprotein inhibitor II Non-inhibitor 0.7509
Renal organic cation transporter Non-inhibitor 0.6957
CYP450 2C9 substrate Non-substrate 0.6516
CYP450 2D6 substrate Non-substrate 0.8178
CYP450 3A4 substrate Substrate 0.5243
CYP450 1A2 substrate Non-inhibitor 0.5153
CYP450 2C9 substrate Inhibitor 0.5078
CYP450 2D6 substrate Non-inhibitor 0.8897
CYP450 2C19 substrate Non-inhibitor 0.514
CYP450 3A4 substrate Non-inhibitor 0.6157
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5638
Ames test Non AMES toxic 0.6181
Carcinogenicity Non-carcinogens 0.8573
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.0305 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.6503
hERG inhibition (predictor II) Non-inhibitor 0.5704
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point220-223U.S. Patent 3,275,635.
Predicted Properties
PropertyValueSource
Water Solubility0.124ALOGPS
logP1.27ALOGPS
logP1.01ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)6.92ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area90.41 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity77.01 m3·mol-1ChemAxon
Polarizability31.29 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

U.S. Patent 3,275,635.

General ReferenceNot Available
External Links
ResourceLink
PubChem Compound9565
PubChem Substance46507076
ChemSpider9190
Therapeutic Targets DatabaseDAP000921
PharmGKBPA164748839
ATC CodesA10BC01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
Acetylsalicylic acidAcetylsalicylic acid increases the effect of sulfonylurea, glycodiazine.
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, glycodiazine.
ClofibrateClofibrate may increase the effect of sulfonylurea, glycodiazine.
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, glycodiazine.
TimololThe beta-blocker, timolol, may decrease symptoms of hypoglycemia.
Food InteractionsNot Available

Targets

1. ATP-sensitive inward rectifier potassium channel 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: other/unknown

Components

Name UniProt ID Details
ATP-sensitive inward rectifier potassium channel 1 P48048 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Guirgis FK, Ghanem MH, Abdel-Hay MM: Comparative study of the hypoglycaemic and antilipolytic effects of four antidiabetic agents administered i.v. Arzneimittelforschung. 1976;26(3):435-7. Pubmed
  4. Greeley SA, Tucker SE, Naylor RN, Bell GI, Philipson LH: Neonatal diabetes mellitus: A model for personalized medicine. Trends Endocrinol Metab. 2010 Apr 28. Pubmed
  5. Pondugula SR, Raveendran NN, Ergonul Z, Deng Y, Chen J, Sanneman JD, Palmer LG, Marcus DC: Glucocorticoid regulation of genes in the amiloride-sensitive sodium transport pathway by semicircular canal duct epithelium of neonatal rat. Physiol Genomics. 2006 Jan 12;24(2):114-23. Epub 2005 Nov 1. Pubmed
  6. Lu M, Leng Q, Egan ME, Caplan MJ, Boulpaep EL, Giebisch GH, Hebert SC: CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney. J Clin Invest. 2006 Mar;116(3):797-807. Epub 2006 Feb 9. Pubmed
  7. Serrano-Martin X, Payares G, Mendoza-Leon A: Glibenclamide, a blocker of K+(ATP) channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis. Antimicrob Agents Chemother. 2006 Dec;50(12):4214-6. Epub 2006 Oct 2. Pubmed

2. ATP-binding cassette sub-family C member 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
ATP-binding cassette sub-family C member 8 Q09428 Details

References:

  1. Dabrowski M, Ashcroft FM, Ashfield R, Lebrun P, Pirotte B, Egebjerg J, Bondo Hansen J, Wahl P: The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener. Diabetes. 2002 Jun;51(6):1896-906. Pubmed
  2. Hambrock A, Preisig-Muller R, Russ U, Piehl A, Hanley PJ, Ray J, Daut J, Quast U, Derst C: Four novel splice variants of sulfonylurea receptor 1. Am J Physiol Cell Physiol. 2002 Aug;283(2):C587-98. Pubmed
  3. Hambrock A, Loffler-Walz C, Quast U: Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides. Br J Pharmacol. 2002 Aug;136(7):995-1004. Pubmed
  4. Nielsen FE, Bodvarsdottir TB, Worsaae A, MacKay P, Stidsen CE, Boonen HC, Pridal L, Arkhammar PO, Wahl P, Ynddal L, Junager F, Dragsted N, Tagmose TM, Mogensen JP, Koch A, Treppendahl SP, Hansen JB: 6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives potently and selectively activate ATP sensitive potassium channels of pancreatic beta-cells. J Med Chem. 2002 Sep 12;45(19):4171-87. Pubmed
  5. Babenko AP, Bryan J: SUR-dependent modulation of KATP channels by an N-terminal KIR6.2 peptide. Defining intersubunit gating interactions. J Biol Chem. 2002 Nov 15;277(46):43997-4004. Epub 2002 Sep 3. Pubmed
  6. Ueda K, Komine J, Matsuo M, Seino S, Amachi T: Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1268-72. Pubmed

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Drug created on July 06, 2007 14:33 / Updated on April 25, 2014 13:49