Repaglinide

Bezeichnung:Repaglinide

CAS-Nr135062-02-1

Englisch Name:Repaglinide

CBNumberCB4140539

SummenformelC27H36N2O4

Molgewicht452.59

MOL-Datei135062-02-1.mol

Repaglinide physikalisch-chemischer Eigenschaften

Schmelzpunkt	129-130.2 °C
alpha	D20 +6.97° (c = 0.975 in methanol); D20 +7.45° (c = 1.06 in methanol)
Siedepunkt	672.9±55.0 °C(Predicted)
Dichte	1.137±0.06 g/cm3(Predicted)
storage temp.	2-8°C
Löslichkeit	DMSO: 34 mg/mL
Aggregatzustand	solid
pka	4.19±0.10(Predicted)
Farbe	white
Wasserlöslichkeit	89.99mg/L(25 ºC)
Merck	14,8136
InChIKey	FAEKWTJYAYMJKF-QHCPKHFHSA-N
SMILES	C(O)(=O)C1=CC=C(CC(N[C@H](C2=CC=CC=C2N2CCCCC2)CC(C)C)=O)C=C1OCC
CAS Datenbank	135062-02-1(CAS DataBase Reference)

Sicherheit

WGK Germany	2
RTECS-Nr.	000000033825
HS Code	2933399090
Toxizität	LD50 orally in rats: >1 g/kg (Grell)

Gefahreninformationscode (GHS)

Repaglinide Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Repaglinide was marketed in the US as an orally active hypoglycemic agent in patients with a type Ⅱ diabetes mellitus, to lower blood glucose in synergistic combination with metformin, when hyperglycemia cannot be controlled by diet, exercise or metformin alone. Chiral (S)-repaglinide can be synthesized in several ways, each involving a stereoselective reduction of an imine or enamine group. Repaglinide is a nonsulfonylurea belonging to the meglitinide family, with an insulin-releasing effect mediated by pancreatic betacells, by closing the ATP-sensitive K+ channels that, in turn, increases the cytosolic concentration of Ca++. In several animal models, repaglinide was more efficient than glibenclamide as a dose-dependant promoter of insulin release, but its mechanism of action is probably slightly different. Repaglinide has a rapid onset of action, a short duration of action and a reduced risk of hypoglycemia compared to glyburide.
Beschreibung
Repaglinide is a metaglitinide antidiabetic agent that blocks ATP-dependent potassium (K_ir6) channels in pancreatic β-cells (K_d = 0.42 nM for the sulphonylurea receptor SUR1 when co-expressed with K_ir6.2). In vivo, repaglinide lowers blood glucose in fasted rats and dogs (ED₅₀s = 10 and 28.3 μg/kg, respectively). Formulations containing repaglinide have been used to control blood sugar levels in patients with type 2 diabetes.
Chemische Eigenschaften
White to Off-White Solid
Originator
Boehringer Ingelheim (Germany)
Verwenden
A KIR6 (KATP) channel blocker
Verwenden
antineoplastic
Verwenden
Non-sulfonylurea oral hypoglycemic agent. Used as an antidiabetic
Verwenden
The R-enantiomer showed only weak hypoglycemic activity. Repaglinide impurity
Definition
ChEBI: Repaglinide is a member of piperidines.
Trademarks
Prandin (Novo Nordisk).
Allgemeine Beschreibung
Repaglinide, (+)-2-ethoxy-4-[N-[3-methyl-1(S)-[2-(1-piperidinyl) phenyl]butyl]carbamoyl-methyl]benzoicacid (Prandin), represents a new class of nonsulfonylureaoral hypoglycemic agents. With a fast onset and ashort duration of action, the medication should be taken withmeals. It is oxidized by CYP 3A4, and the carboxylic acidmay be conjugated to inactive compounds. Less than 0.2%is excreted unchanged by the kidney, which may be an advantagefor elderly patients who are renally impaired. Themost common side effect involves hypoglycemia, resultingin shakiness, headache, cold sweats, anxiety, and changes inmental state.
Allgemeine Beschreibung
Repaglinide is 2-ethoxy-4-[2-[[(1S)-3-methyl-1-[2-(1-piperidinyl)phenyl]butyl]amino]-2-oxoethyl]benzoic acid(Prandin); approvals for generics are pending. Combinationsare available with metformin in the United States(Prandimet), and the drug may also be coprescribed with oneof the thiazolidinediones (typically pioglitazone or rosiglitazone;see previous discussion). To establish the most clinicallyvaluable dose, the patient is titrated while monitoringblood glucose levels and hemoglobin glycosylation (HbA1c)as an index of longer-term overall control.
Biologische Aktivität
K ATP channel blocker that binds with high affinity for SUR1 when co-expressed with Kir6.2 (K d = 0.42 nM). Antidiabetic glucose regulator with hypoglycaemic effect in vivo .
Biochem/physiol Actions
Repaglinide is a potent short-acting insulin secretagogue that acts by closing ATP-sensitive potassium (KATP) channels in the plasma membrane of the pancreatic beta cell. It represents a new class of insulin secretagogues, structurally unrelated to sulphonylureas, which were developed for the treatment of type 2 diabetes.
Clinical Use
Repaglinide is a nonsulfonylurea insulin secretagogue that was introduced in the United States in 1998 for type 2 diabetes.
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Antibacterials: effects enhanced by clarithromycin and possibly trimethoprim - avoid with trimethoprim; hypoglycaemic effect antagonised by rifampicin.
Antifungals: effect possibly enhanced by itraconazole.
Ciclosporin: may increase repaglinide concentration, possibly enhanced hypoglycaemic effect.
Clopidogrel: avoid concomitant use if possible due to increased repaglinide exposure.
Cytotoxics: avoid with lapatinib.
Lipid-lowering agents: increased risk of severe hypoglycaemia with gemfibrozil - avoid.
Stoffwechsel
Repaglinide appears to be a substrate for active hepatic uptake by the organic anion transporting protein OATP1B1, and undergoes almost complete hepatic metabolism involving the cytochrome P450 isoenzymes CYP2C8 and CYP3A4. The glucuronidation of repaglinide is thought to involve uridine diphosphate glucuronosyltransferase (UGT) enzymes, particularly UGT1A1.
The metabolites, which are inactive, are excreted in the bile.
Lager
+4°C

Repaglinide Upstream-Materialien And Downstream Produkte

Repaglinide Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

135062-02-1, Repaglinide Verwandte Suche:

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