Glibenclamid

Bezeichnung:Glibenclamid

CAS-Nr10238-21-8

Englisch Name:Glibenclamide

CBNumberCB1737679

SummenformelC23H28ClN3O5S

Molgewicht494

MOL-Datei10238-21-8.mol

Synonyma

Glibenclamid

Glibenclamid physikalisch-chemischer Eigenschaften

Schmelzpunkt	173-175°C
Dichte	1.1805 (rough estimate)
Brechungsindex	1.6100 (estimate)
storage temp.	2-8°C
Löslichkeit	ethanol: soluble2mg/mL
Aggregatzustand	White solid
pka	5.3(at 25℃)
Farbe	White
Wasserlöslichkeit	Soluble in ethanol (5 mg/mL), DMSO (25 mg/mL), chloroform (1:36), methanol (1:250), and DMF. Insoluble in water.
Merck	14,4478
BCS Class	2
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
InChIKey	ZNNLBTZKUZBEKO-UHFFFAOYSA-N
CAS Datenbank	10238-21-8(CAS DataBase Reference)
NIST chemische Informationen	Glyburide(10238-21-8)
EPA chemische Informationen	Benzamide, 5-chloro-N-[2-[4-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]phenyl]ethyl]-2-methoxy- (10238-21-8)

Sicherheit

Kennzeichnung gefährlicher	Xn
R-Sätze:	20/21/22
S-Sätze:	22-36/37/39-36-24/25
WGK Germany	2
RTECS-Nr.	YS4725200
HS Code	29350090
Toxizität	LD50 in rats and mice (g/kg): >20 orally; >12.5 i.p.; >20 s.c. (Mizukami)

Gefahreninformationscode (GHS)

Glibenclamide Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R20/21/22:Gesundheitsschädlich beim Einatmen,Verschlucken und Berührung mit der Haut.
S-Sätze Betriebsanweisung:
S22:Staub nicht einatmen.
S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
Beschreibung
Glyburide (10238-21-8) is a second generation oral hypoglycemic agent. Acts via ATP-dependent K+ channel (Kir6, KATP) block.1?Inhibits Kir6 currents in the pancreas, causing an increase in intracellular Ca2+ and insulin secretion. Glyburide also inhibits recombinant CFTR Cl- channels with an IC50 of 20 μM.2?Cell permeable.
Chemische Eigenschaften
White or almost white, crystalline powder
Originator
Daonil,Hoechst,Germany
Verwenden
An ATP-dependent KIR6 and CFTR Cl- channel blocker
Verwenden
antihyperglycemic
Verwenden
Glyburide (Glibenclamide) is a sulfonylurea compound that modulates insulin production. Sulfonylureas bind to ATP-dependent K+ channels in beta cells of the pancreas, depolarizing them and stimulating the release of Ca2+, which in turn stimulates insulin production. Glyburide (Glibenclamide) is an ATP-dependent K+ channel (KIR6, KATP) and CFTR Cl- channel blocker. This compound inhibits recombinant CFTR Cl- channels (IC50 = 20 ?M).
Verwenden
Glyburide is a second generation sulfonylurea with hypoglycemic activity. Glyburide is an antidiabetic.
Definition
ChEBI: An N-sulfonylurea that is acetohexamide in which the acetyl group is replaced by a 2-(5-chloro-2-methoxybenzamido)ethyl group.
Manufacturing Process
To a solution of 10.2 g of 4-(β-(2-ethoxy-5-chlorobenzamido)ethyl)- benzenesulfonamide in 12.5 ml of 2 N sodium hydroxide solution and 30 ml acetone are added dropwise, at 0-5°C, 3.3 g of cyclohexyl isocyanate. The whole is stirred for 3 hours, diluted with water and methanol, undissolved matter is separeted by filtration. The filtrate is acidified with dilute hydrochloric acid. The 4-(β-(2-ethoxy-5-chlorobenzamido)ethyl)- benzenesulfonyl)-N'-cyclohexylurea which precipitates in the form of crystals melts after recrystallization from methanol at 168-170°C.
Trademarks
Micronase (Pharmacia & Upjohn).
Therapeutic Function
Oral hypoglycemic
Allgemeine Beschreibung
Similar to glipizide, glyburide, 1-[[p-[2-(5-chloro-o-anisamido)ethyl]-phenyl]sulfonyl]-3-cyclohexylurea(DiaBeta, Micronase, Glynase), is a second-generationoral hypoglycemic agent. The drug has a half-life eliminationof 10 hours, but its hypoglycemic effect remains for upto 24 hours.
Allgemeine Beschreibung
Glyburide (glibenclamide) is 5-chloro-N-[2-[4-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]phenyl]ethyl]-2-methoxybenzamide; this compound can also be named asthe urea—see preceding discussion (Diabeta, Glynase,generic). Some tablet formulations contain micronized drug(formerly Micronase, now only generic). Combinations areavailable with metformin in the United States (Glucovance,generic; tablets, mg glipizide/mg metformin as hydrochloride:1.25/250, 2.5/500, 5/500).
Biologische Aktivität
ATP-dependent K + channel (K ATP ) and CFTR Cl - channel blocker. Inhibits K ATP currents in the pancreas, causing an increase in intracellular Ca 2+ and insulin secretion. Inhibits recombinant CFTR Cl- channels with an IC 50 of 20 μ M.
Biochem/physiol Actions
Selectively blocks ATP-sensitive K+ channels; high affinity binding sites found in brain, pancreatic β cells, and cardiovascular system.
Mechanism of action
This drug belongs to the second-generation sulfonylurea derivatives. Like all of the other oral hypoglycemic drugs examined, it is a β-cell stimulant in pancreas; but on the other hand, it increases the sensitivity to insulin, the degree to which it binds with target cells. At the same time, it differs in that it is easier to tolerate. The hypoglycemic effect sets in at significantly lower doses than with first-generation drugs.
Clinical Use
Non-insulin dependent diabetes mellitus
Synthese
Glyburide, 1-[4-[2-(5-chloro-2-methoxybenzamido)ethyl]-phenylsulfonyl]-3- cyclohexylurea (26.2.11), is a second-generation drug that differs from those described above in that it has a more complex structure in the sulfonylamide region of the molecule into which an additional pharmacophore group is added. It is synthesized from 2-methoxy-5-chlorobenzoic acid chloride, which is transformed into an amide 26.2.9 by reacting it with 2-phenylethylamine. This undergoes subsequent sulfonylchlorination by chlorosulfonic acid, and then amination by ammonia, which gives sulfonamide 26.2.10. The resulting sulfonamide is reacted with cylclohexylisocyanate to give the desired glyburide (26.2.11).
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Analgesics: effects enhanced by NSAIDs.
Antibacterials: effects enhanced by chloramphenicol, sulphonamides, tetracyclines and trimethoprim; effects possibly enhanced by ciprofloxacin and norfloxacin; effect reduced by rifamycins.
Anticoagulants: effect possibly enhanced by coumarins; also possibly changes to INR.
Antifungals: concentration increased by fluconazole and miconazole and possibly voriconazole.
Bosentan: increased risk of hepatoxicity - avoid.
Ciclosporin: may increase ciclosporin levels.
Lipid-regulating drugs: absorption reduced by colesevelam; concentration possibly increased by fluvastatin; possibly additive hypoglycaemic effect with fibrates.
Sulfinpyrazone: enhanced effect of sulphonylureas.
Stoffwechsel
Glibenclamide is metabolised, almost completely, in the liver, the principal metabolite being only very weakly active.
About 50% of a dose is excreted in the urine and 50% via the bile into the faeces.
Lager
Store at RT
Einzelnachweise
1) Brogden et al. (1979), Glipizide: a review of its pharmacological properties and therapeutic use; Drugs, 18 329 2) Sheppard and Welsh (1992), Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents; J. Gen. Physiol., 100 573

Glibenclamide Upstream-Materialien And Downstream Produkte

Glibenclamid Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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