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targets (2)
for drugs
Identification
Name Glycodiazine
Accession Number DB01382
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Glidiazine
Glymidine
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Hypoglycemic Agents
CAS number 339-44-6
Weight Average: 309.341
Monoisotopic: 309.078326673
Chemical Formula C13H15N3O4S
InChI Key InChIKey=QFWPJPIVLCBXFJ-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)
Plain Text
IUPAC Name
N-[5-(2-methoxyethoxy)pyrimidin-2-yl]benzenesulfonamide
SMILES
COCCOC1=CN=C(NS(=O)(=O)C2=CC=CC=C2)N=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzenesulfonamides
Substructures
  • Sulfonyls
  • Ethers
  • Benzene and Derivatives
  • Benzenesulfonamides
  • Pyrimidines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Sulfonamides
  • Cyanamides
Pharmacology
Indication Glycodiazine is used concomitantly with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.
Pharmacodynamics 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.
Mechanism of action 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. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.
Absorption Rapidly and completely absorbed following oral administration.
Volume of distribution Not Available
Protein binding 90% bound to plasma proteins.
Metabolism Not Available
Route of elimination Not Available
Half life 4 hours.
Clearance Not Available
Toxicity Severe hypoglycemic reactions with coma, seizure, or other neurological impairment.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms
Form Route Strength
Tablet Oral
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 153 °C PhysProp
Predicted Properties
Property Value Source
water solubility 1.24e-01 g/l ALOGPS
logP 1.27 ALOGPS
logP 1.01 ChemAxon
logS -3.4 ALOGPS
pKa (strongest acidic) 6.92 ChemAxon
pKa (strongest basic) -1.4 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 90.41 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 77.01 ChemAxon
polarizability 31.29 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PubChem Compound 9565 Link_out
PubChem Substance 46507076 Link_out
ChemSpider 9190 Link_out
Therapeutic Targets Database DAP000921 Link_out
PharmGKB PA164748839 Link_out
ATC Codes
  • A10BC01
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Acetylsalicylic acid Acetylsalicylic acid increases the effect of sulfonylurea, glycodiazine.
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, glycodiazine.
Clofibrate Clofibrate may increase the effect of sulfonylurea, glycodiazine.
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, glycodiazine.
Timolol The beta-blocker, timolol, may decrease symptoms of hypoglycemia.
Food Interactions Not Available
Targets

1. ATP-sensitive inward rectifier potassium channel 1

Pharmacological action: yes
Actions: other/unknown

In the kidney, probably plays a major role in potassium homeostasis. 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. This channel is activated by internal ATP and can be blocked by external barium

Organism class: human
UniProt ID: P48048 Link_out
Gene: KCNJ1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 transporter sub-family C member 8

Pharmacological action: unknown
Actions: inducer

Putative subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K+ channels and insulin release

Organism class: human
UniProt ID: Q09428 Link_out
Gene: ABCC8 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on July 06, 2007 14:33 / Updated on February 08, 2013 16:20