You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
Glurenorm
External Identifiers Not Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
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
SaltsNot Available
Categories
UNIIC7C2QDD75P
CAS number33342-05-1
WeightAverage: 527.632
Monoisotopic: 527.209006493
Chemical FormulaC27H33N3O6S
InChI KeyInChIKey=LLJFMFZYVVLQKT-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
1-cyclohexyl-3-{4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]benzenesulfonyl}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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 1,3-isoquinolinediones. These are isoquinoline derivatives carrying one C=O group at positions 1, and 3 respectively.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIsoquinolines and derivatives
Sub Class1,3-isoquinolinediones
Direct Parent1,3-isoquinolinediones
Alternative Parents
Substituents
  • 1,3-isoquinolinedione
  • Isoquinolone
  • Tetrahydroisoquinoline
  • Benzenesulfonamide
  • Phenethylamine
  • Anisole
  • Sulfonylurea
  • Dicarboximide
  • Cyclohexylamine
  • Alkyl aryl ether
  • Benzenoid
  • Monocyclic benzene moiety
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Tertiary amine
  • Carboxamide group
  • Azacycle
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
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
MetabolismNot Available
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
PropertyValueProbability
Human Intestinal Absorption+0.9157
Blood Brain Barrier+0.625
Caco-2 permeable-0.6185
P-glycoprotein substrateSubstrate0.7457
P-glycoprotein inhibitor IInhibitor0.6115
P-glycoprotein inhibitor IIInhibitor0.805
Renal organic cation transporterNon-inhibitor0.7921
CYP450 2C9 substrateSubstrate0.5166
CYP450 2D6 substrateNon-substrate0.8162
CYP450 3A4 substrateSubstrate0.594
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.6454
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.7961
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5173
Ames testNon AMES toxic0.6124
CarcinogenicityNon-carcinogens0.7477
BiodegradationNot ready biodegradable0.8693
Rat acute toxicity2.3506 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8418
hERG inhibition (predictor II)Inhibitor0.6182
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
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 Solubility0.0022 mg/mLALOGPS
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 Area121.88 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity139.48 m3·mol-1ChemAxon
Polarizability57.26 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

U.S. Patent 3,708,486.

General ReferencesNot Available
External Links
ATC CodesA10BB08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AripiprazoleThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Aripiprazole.
Arsenic trioxideThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Arsenic trioxide.
ArticaineThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Articaine.
AsenapineThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Asenapine.
AtazanavirThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Atazanavir.
BendroflumethiazideThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Bendroflumethiazide.
BetamethasoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Betamethasone.
BrexpiprazoleThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Brexpiprazole.
BumetanideThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Bumetanide.
BuserelinThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Buserelin.
CeritinibThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Ceritinib.
ChlorothiazideThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Chlorothiazide.
ChlorpropamideGliquidone may increase the hypoglycemic activities of Chlorpropamide.
ChlorthalidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Chlorthalidone.
ClozapineThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Clozapine.
CorticotropinThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Corticotropin.
Cortisone acetateThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Cortisone acetate.
Cyproterone acetateThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Cyproterone acetate.
DabrafenibThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Dabrafenib.
DanazolThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Danazol.
DarunavirThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Darunavir.
DesogestrelThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Desogestrel.
DexamethasoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Dexamethasone.
DiazoxideThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Diazoxide.
DienogestThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Dienogest.
DisopyramideGliquidone may increase the hypoglycemic activities of Disopyramide.
DrospirenoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Drospirenone.
EpinephrineThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Epinephrine.
ErythromycinGliquidone may increase the hypoglycemic activities of Erythromycin.
EstradiolThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Estradiol.
EstropipateThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Estropipate.
Ethacrynic acidThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Ethacrynic acid.
Ethinyl EstradiolThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Ethinyl Estradiol.
EthynodiolThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Ethynodiol.
EtonogestrelThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Etonogestrel.
EverolimusThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Everolimus.
FludrocortisoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Fludrocortisone.
FosamprenavirThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Fosamprenavir.
FurosemideThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Furosemide.
GliclazideGliquidone may increase the hypoglycemic activities of Gliclazide.
GlimepirideGliquidone may increase the hypoglycemic activities of Glimepiride.
GlipizideGliquidone may increase the hypoglycemic activities of Glipizide.
GlyburideGliquidone may increase the hypoglycemic activities of Glyburide.
GoserelinThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Goserelin.
HistrelinThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Histrelin.
HydrochlorothiazideThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Hydrochlorothiazide.
HydrocortisoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Hydrocortisone.
Hydroxyprogesterone caproateThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Hydroxyprogesterone caproate.
IloperidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Iloperidone.
IndapamideThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Indapamide.
IndinavirThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Indinavir.
inhaled insulinGliquidone may increase the hypoglycemic activities of inhaled insulin.
Insulin AspartGliquidone may increase the hypoglycemic activities of Insulin Aspart.
Insulin degludecGliquidone may increase the hypoglycemic activities of Insulin degludec.
Insulin DetemirGliquidone may increase the hypoglycemic activities of Insulin Detemir.
Insulin GlargineGliquidone may increase the hypoglycemic activities of Insulin Glargine.
Insulin GlulisineGliquidone may increase the hypoglycemic activities of Insulin Glulisine.
Insulin LisproGliquidone may increase the hypoglycemic activities of Insulin Lispro.
Insulin RegularGliquidone may increase the hypoglycemic activities of Insulin Regular.
LanreotideGliquidone may increase the hypoglycemic activities of Lanreotide.
LeuprolideThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Leuprolide.
LevonorgestrelThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Levonorgestrel.
LopinavirThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Lopinavir.
LurasidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Lurasidone.
MecaserminGliquidone may increase the hypoglycemic activities of Mecasermin.
Medroxyprogesterone AcetateThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Medroxyprogesterone Acetate.
Megestrol acetateThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Megestrol acetate.
MestranolThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Mestranol.
MethotrimeprazineThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Methotrimeprazine.
MethyclothiazideThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Methyclothiazide.
MethylprednisoloneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Methylprednisolone.
MetolazoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Metolazone.
MifepristoneGliquidone may increase the hypoglycemic activities of Mifepristone.
NadololThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Nadolol.
NateglinideGliquidone may increase the hypoglycemic activities of Nateglinide.
NelfinavirThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Nelfinavir.
NiacinThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Niacin.
NilotinibThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Nilotinib.
NorethindroneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Norethindrone.
NorgestimateThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Norgestimate.
OctreotideGliquidone may increase the hypoglycemic activities of Octreotide.
OlanzapineThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Olanzapine.
PaliperidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Paliperidone.
PasireotideGliquidone may increase the hypoglycemic activities of Pasireotide.
PentamidineGliquidone may increase the hypoglycemic activities of Pentamidine.
PipotiazineThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Pipotiazine.
PrednisoloneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Prednisolone.
PrednisoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Prednisone.
ProgesteroneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Progesterone.
QuetiapineThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Quetiapine.
QuinineGliquidone may increase the hypoglycemic activities of Quinine.
RepaglinideGliquidone may increase the hypoglycemic activities of Repaglinide.
Repository corticotropinThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Repository corticotropin.
RisperidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Risperidone.
RitonavirThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Ritonavir.
SaquinavirThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Saquinavir.
SirolimusThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Sirolimus.
SulfadiazineGliquidone may increase the hypoglycemic activities of Sulfadiazine.
SulfamethoxazoleGliquidone may increase the hypoglycemic activities of Sulfamethoxazole.
SulfisoxazoleGliquidone may increase the hypoglycemic activities of Sulfisoxazole.
SunitinibGliquidone may increase the hypoglycemic activities of Sunitinib.
TacrolimusThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Tacrolimus.
TemsirolimusThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Temsirolimus.
TipranavirThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Tipranavir.
TolazamideGliquidone may increase the hypoglycemic activities of Tolazamide.
TolbutamideGliquidone may increase the hypoglycemic activities of Tolbutamide.
TorasemideThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Torasemide.
TriamcinoloneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Triamcinolone.
TrimethoprimGliquidone may increase the hypoglycemic activities of Trimethoprim.
TriptorelinThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Triptorelin.
VorinostatThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Vorinostat.
ZiprasidoneThe therapeutic efficacy of Gliquidone can be decreased when used in combination with Ziprasidone.
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

Comments
comments powered by Disqus
Drug created on March 30, 2007 08:35 / Updated on April 25, 2014 11:50