Linagliptin

Bezeichnung:Linagliptin

CAS-Nr668270-12-0

Englisch Name:Linagliptin

CBNumberCB71518518

SummenformelC25H28N8O2

Molgewicht472.54

MOL-Datei668270-12-0.mol

Linagliptin physikalisch-chemischer Eigenschaften

Schmelzpunkt	202 ºC
Siedepunkt	661.2±65.0 °C(Predicted)
Dichte	1.39
storage temp.	Refrigerator
Löslichkeit	Chloroform (Sparingly), DMSO (Slightly), Methanol (Slightly)
pka	10.01±0.20(Predicted)
Aggregatzustand	Solid
Farbe	White to Orange
InChIKey	LTXREWYXXSTFRX-QGZVFWFLSA-N
SMILES	N1(CC#CC)C2=C(N(C)C(=O)N(CC3=NC(C)=C4C(=N3)C=CC=C4)C2=O)N=C1N1CCC[C@@H](N)C1

Sicherheit

HS Code	29335990
Giftige Stoffe Daten	668270-12-0(Hazardous Substances Data)

Gefahreninformationscode (GHS)

Linagliptin Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Linagliptin (trade names Tradjenta and Trajetna) is an inhibitor of dipeptidyl peptidase-4 (DPP-4) that was approved by the U.S. FDA in May 2011 for the treatment of Type 2 diabetes along with diet and exercise. Linagliptin (BI-1356) has been described as a potent highly selective, slow-off rate and long acting inhibitor of DPP-4. Linagliptin arose from optimization efforts of xanthine-based DPP-4 inhibitors with the initial lead identified from an HTS campaign. After optimizing the activity of the initial micromolar lead, two issues that needed to be addressed were activity for hERG and muscarinic receptor M1. Introduction of a butynyl group at the N7 position of the xanthine ring gave much reduced M1 affinity with no measureable hERG activity. Linagliptin inhibits DPP-4 with an IC₅₀=1 nM and is highly selective (>10,000-fold) against DPP-8 and DPP-9. Linagliptin shows no interactions with CYPs up to 50 mM. The described synthesis of linagliptin starts with 8-bromoxanthine, which is alkylated at the N-7 position to introduce the butyne group, followed by alkylation of the N-1 group to introduce the methyl-quinazoline group. Displacement of the bromide with (R)-Boc-3-amino-piperidine followed by deprotection gives linagliptin. When administered to db/db mice orally, linagliptin dose dependently reduced glucose excursion from 0.1 mg/kg (15% inhibition) to 1 mg/kg (66% inhibition).
Originator
Boehringer Ingelheim (United States)
Verwenden
dipeptidypeptidase inhibitor, antidiabetic
Verwenden
A novel potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor with potential use in the treatment of type 2 diabetes.
Verwenden
Labeled Linagliptin, intended for use as an internal standard for the quantification of Linagliptin by GC- or LC-mass spectrometry.
Verwenden
highly potent CD26 inhibitor
Definition
ChEBI: A xanthine that is 7H-xanthine bearing (4-methylquinazolin-2-yl)methyl, methyl, but-2-yn-1-yl and 3-aminopiperidin-1-yl substituents at positions 1, 3, 7 and 8 respectively (the R-enantiomer). Used for treatment of type I diabetes.
Trademarks
Tradjenta
Clinical Use
Type 2 diabetes mellitus
Synthese
The synthesis of linagliptin began from commercially available 8-bromo-3-methylxanthine (171). Sequential alkylations of guanine derivative 171 at N-7 with butyn-2-yl bromide in the presence of N,N-diisopropylethylamine and N-1 with 2- (chloromethyl)-4-methylquinazoline (173) in the presence of potassium carbonate, yielded N1,N7-dialkylated xanthine 174 in 85% yield. This material was further condensed with (R)-3-Bocaminopiperidine (175) in the presence of potassium carbonate to give aminopurine dione 176 in 88% yield. Finally, the primary amine of 176 was liberated with trifluoroacetic acid in methylene chloride to produce linagliptin (XV) in 91% yield.
target
DDP-4
Lager
+4°C

Linagliptin Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

668270-12-0, Linagliptin Verwandte Suche:

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