Nateglinide

Bezeichnung:Nateglinide

CAS-Nr105816-04-4

Englisch Name:Nateglinide

CBNumberCB9472923

SummenformelC19H27NO3

Molgewicht317.42

MOL-Datei105816-04-4.mol

Nateglinide physikalisch-chemischer Eigenschaften

Schmelzpunkt	137-141°C
alpha	D20 -9.4° (c = 1 in methanol)
Siedepunkt	527.6±39.0 °C(Predicted)
Dichte	1.104±0.06 g/cm3(Predicted)
storage temp.	room temp
Löslichkeit	DMSO: >5mg/mL
pka	3.61±0.10(Predicted)
Aggregatzustand	solid
Farbe	white to off-white
Merck	14,6428
CAS Datenbank	105816-04-4(CAS DataBase Reference)

Sicherheit

Kennzeichnung gefährlicher	Xn
R-Sätze:	22
S-Sätze:	24/25-36
WGK Germany	3
RTECS-Nr.	SQ7318950
HS Code	29242990
Toxizität	LD50 orally in rats: >2.0 g/kg (Hasegawa)

Gefahreninformationscode (GHS)

Nateglinide Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
S-Sätze Betriebsanweisung:
S24/25:Berührung mit den Augen und der Haut vermeiden.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
Beschreibung
Nateglinide is a N-acylated D-phenylalanine marketed in Japan as novel orally active insulinotropic agent for the treatment of type-2 diabetes mellitus. It belongs to the class of nonsulfonylureas and shows some structural similarity to repaglinide, the only other representative in this family. In single pancreatic beta-cells isolated from rats, Nateglinide was found to specifically block the ATP-sensitive K+ channel resulting in an increase in intracellular calcium concentration. This primary action would underlie the mechanism by which Nateglinide markedly stimulates or potentiates, depending on glucose concentrations, insulin secretion from pancreatic beta-cells. Clinical studies demonstrated a good safety profile with a low potential for hypoglycemia. The pharmacokinetic profile was consistent with the changes of the blood glucose and plasma insulin level. Interestingly, Nateglinide exerts a rapid onset and short duration of action due to a rapid absorption and clearance. Unlike other similar agents, Nateglinide suppresses postprandial glucose elevations.
Chemische Eigenschaften
Cyrstalline Solid
Originator
Ajinomoto (Japan)
Verwenden
An amino-acid derivative that stimulates insulin secretion. Used as an antidiabetic.
Verwenden
antidiabetic KATP channel blocker
Definition
ChEBI: An N-acyl-D-phenylalanine resulting from the formal condensation of the amino group of D-phenylalanine with the carboxy group of trans-4-isopropylcyclohexanecarboxylic acid. An orally-ad inistered, rapidly-absorbed, short-acting insulinotropic agent, it is used for the treatment of type 2 diabetes mellitus.
Trademarks
Starlix (Novartis);Fastic;Starsis.
Allgemeine Beschreibung
Although nateglinide, N-(4-isopropylcyclohexanecarbonyl)-D-phenylalanine (Starlix), belongs tothe metaglinides, it is a phenylalanine derivative and representsa novel drug in the management of type 2 diabetes.
Allgemeine Beschreibung
Nateglinide (Starlix) is D-Phenylalanine, N-[[trans-4-(1-methylethyl)cyclohexyl]carbonyl]-; or (-)-N-[(trans-4-isopropylcyclohexyl)carbonyl]-D-phenylalanine. Itis noteworthy that, although nateglinide is much less potenton a dosage basis than is repaglinide and most of the sulfonylureas,this drug seems to exhibit unique molecularpharmacodynamics. Nateglinide closes ATP-sensitive K channels some threefold more rapidly than repaglinide, andexhibits an off-rate twice as fast as that of glyburide orglimepiride and five times faster than repaglinide. Thesecharacteristics are reflected by the systemic pharmacodynamicsof this drug, translating clinically to improvedsafety, among other apparent benefits.
Biochem/physiol Actions
Nateglinide is a Kir6.2/SUR1 channel inhibitor and antidiabetic. It is selective for the SUR1 subtype, which is found on pancreatic islet cells. Nateglinide evokes KATP channel-dependent insulin secretion (50-200 μM) in the absence and presence of insulin.
Mechanism of action
Approved in the United States in late 2000, nateglinide is a rapidly absorbed insulin secretagogue that has a mechanism of action similar to that of repaglinide, with effects appearing within 20 minutes following oral dosing. Bioavailability is 73%, and it is 98% protein bound, primarily to albumin. Nateglinide is tissue selective, with low affinity for cardiac and skeletal muscle.
Clinical Use
Treatment of type 2 diabetes in combination with metformin
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Antibacterials: concentration reduced by rifampicin.
Antifungals: hypoglycaemic effect possibly enhanced by fluconazole.
Lipid-lowering agents: hypoglycaemic effect possibly enhanced by gemfibrozil.
Stoffwechsel
It is metabolized in the liver, with 16% excreted in the urine unchanged. The major metabolites are hydroxyl derivatives (CYP2C9, 70%; CYP3A4, 30%) that are further conjugated to the glucuronide derivatives.
Lager
Store at RT

Nateglinide Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

105816-04-4, Nateglinide Verwandte Suche:

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