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Identification
NameGliquidone
Accession NumberDB01251
Typesmall molecule
Groupsapproved
Description

Gliquidone is an anti-diabetic drug in the sulfonylurea class. It is used in the treatment of diabetes mellitus type 2. It is an ATP-dependent K+ (KATP) channel blocker. This block causes a depolarization which leads to activation of voltage-dependent Ca channels and Ca2+ influx, and eventually increases insulin release.

Structure
Thumb
Synonyms
SynonymLanguageCode
GlurenormNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
DevotanMenarini
FordiabHexpharm Jaya
GlidiabSoho
GlunormalYing Yuan
GlurenorGuidotti
GlurenormBoehringer Ingelheim
Jie ShiTianjin Institute of Pharmaceutical Research Pharmaceutical
Ka Rui LinAnjielun
LodemDexa Medica
Brand mixturesNot Available
Categories
CAS number33342-05-1
WeightAverage: 527.632
Monoisotopic: 527.209006493
Chemical FormulaC27H33N3O6S
InChI KeyLLJFMFZYVVLQKT-UHFFFAOYSA-N
InChI
InChI=1S/C27H33N3O6S/c1-27(2)23-14-11-20(36-3)17-22(23)24(31)30(25(27)32)16-15-18-9-12-21(13-10-18)37(34,35)29-26(33)28-19-7-5-4-6-8-19/h9-14,17,19H,4-8,15-16H2,1-3H3,(H2,28,29,33)
IUPAC Name
3-cyclohexyl-1-({4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]benzene}sulfonyl)urea
SMILES
COC1=CC2=C(C=C1)C(C)(C)C(=O)N(CCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1)C2=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassIsoquinolines and Derivatives
SubclassIsoquinolones and Derivatives
Direct parentIsoquinolones and Derivatives
Alternative parentsPhenethylamines; Anisoles; Sulfonylureas; Alkyl Aryl Ethers; N-substituted Carboxylic Acid Imides; Tertiary Carboxylic Acid Amides; Sulfonamides; Sulfonyls; Tertiary Amines; Carboxylic Acids; Polyamines
Substituentsphenethylamine; anisole; phenol ether; alkyl aryl ether; sulfonylurea; carboxylic acid imide, n-substituted; benzene; sulfonic acid derivative; sulfonyl; tertiary carboxylic acid amide; sulfonamide; carboxylic acid imide; carboxamide group; tertiary amine; carboxylic acid; ether; polyamine; carboxylic acid derivative; amine; organonitrogen compound
Classification descriptionThis compound belongs to the isoquinolones and derivatives. These are aromatic polycyclic compounds containing a ketone bearing isoquinoline moiety.
Pharmacology
IndicationUsed in the treatment of diabetes mellitus type 2.
PharmacodynamicsGliquidone is an anti-diabetic drug in the sulfonylurea class. In patients with diabetes mellitus, there is a deficiency or absence of a hormone manufactured by the pancreas called insulin. Insulin is the main hormone responsible for the control of sugar in the blood. Gliquidone is an antidiabetic medication which is used in those patients with adult maturity onset or non-insulin dependent diabetes (NIDDM). It works by lowering blood sugar levels by stimulating the production and release of insulin from the pancreas. It also promotes the movement of sugar from the blood into the cells in the body which need it.
Mechanism of actionThe mechanism of action of gliquidone 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. Gliquidone 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeThe mean terminal half-life was approximately 8 hours (range 5.7-9.4 hours)
ClearanceNot Available
ToxicityNot Available
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 + 0.9157
Blood Brain Barrier + 0.625
Caco-2 permeable - 0.6185
P-glycoprotein substrate Substrate 0.7457
P-glycoprotein inhibitor I Inhibitor 0.6115
P-glycoprotein inhibitor II Inhibitor 0.805
Renal organic cation transporter Non-inhibitor 0.7921
CYP450 2C9 substrate Substrate 0.5166
CYP450 2D6 substrate Non-substrate 0.8162
CYP450 3A4 substrate Substrate 0.594
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.6454
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Inhibitor 0.7961
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5173
Ames test Non AMES toxic 0.6124
Carcinogenicity Non-carcinogens 0.7477
Biodegradation Not ready biodegradable 0.8693
Rat acute toxicity 2.3506 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8418
hERG inhibition (predictor II) Inhibitor 0.6182
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point180-182U.S. Patent 3,708,486.
logP4.5Not Available
Predicted Properties
PropertyValueSource
water solubility2.20e-03 g/lALOGPS
logP3.59ALOGPS
logP4.14ChemAxon
logS-5.4ALOGPS
pKa (strongest acidic)4.32ChemAxon
pKa (strongest basic)-4.8ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count6ChemAxon
hydrogen donor count2ChemAxon
polar surface area121.88ChemAxon
rotatable bond count6ChemAxon
refractivity139.48ChemAxon
polarizability57.26ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

U.S. Patent 3,708,486.

General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD02430
PubChem Compound91610
PubChem Substance46508425
ChemSpider82719
Therapeutic Targets DatabaseDAP000924
PharmGKBPA164744895
WikipediaGliquidone
ATC CodesA10BB08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

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

References:

  1. Gribble FM, Ashcroft FM: Sulfonylurea sensitivity of adenosine triphosphate-sensitive potassium channels from beta cells and extrapancreatic tissues. Metabolism. 2000 Oct;49(10 Suppl 2):3-6. Pubmed
  2. Harrower A: Gliclazide modified release: from once-daily administration to 24-hour blood glucose control. Metabolism. 2000 Oct;49(10 Suppl 2):7-11. Pubmed
  3. Lawrence CL, Proks P, Rodrigo GC, Jones P, Hayabuchi Y, Standen NB, Ashcroft FM: Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells. Diabetologia. 2001 Aug;44(8):1019-25. Pubmed
  4. Reimann F, Ashcroft FM, Gribble FM: Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes. 2001 Oct;50(10):2253-9. Pubmed
  5. Proks P, Reimann F, Green N, Gribble F, Ashcroft F: Sulfonylurea stimulation of insulin secretion. Diabetes. 2002 Dec;51 Suppl 3:S368-76. Pubmed

2. ATP-sensitive inward rectifier potassium channel 8

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
ATP-sensitive inward rectifier potassium channel 8 Q15842 Details

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
  3. Hill RA, Rudra S, Peng B, Roane DS, Bounds JK, Zhang Y, Adloo A, Lu T: Hydroxyl-substituted sulfonylureas as potent inhibitors of specific [3H]glyburide binding to rat brain synaptosomes. Bioorg Med Chem. 2003 May 1;11(9):2099-113. Pubmed

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Drug created on March 30, 2007 08:35 / Updated on April 25, 2014 11:50