ALOGLIPTIN(ALOGLIPTINE, ALOGLIPTINA) Chemical Properties

Melting point:

127 - 129°C

Boiling point:

519.2±60.0 °C(Predicted)

Density 

1.342

Flash point:

267.8℃

storage temp. 

Refrigerator

solubility 

Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)

pka

9.89±0.20(Predicted)

form 

Solid

color 

White to Off-White

InChI

InChI=1S/C18H21N5O2/c1-21-17(24)9-16(22-8-4-7-15(20)12-22)23(18(21)25)11-14-6-3-2-5-13(14)10-19/h2-3,5-6,9,15H,4,7-8,11-12,20H2,1H3/t15-/m1/s1

InChIKey

ZSBOMTDTBDDKMP-OAHLLOKOSA-N

SMILES

C(#N)C1=CC=CC=C1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1

Safety Information

Safety Statements 

24/25

RIDADR 

3077

HS Code 

29335990

Hazardous Substances Data

850649-61-5(Hazardous Substances Data)

ALOGLIPTIN(ALOGLIPTINE, ALOGLIPTINA) Usage And Synthesis

Description

Alogliptin is a dipeptidyl-peptidase IV (DPP-4) inhibitor that was approved in Japan in 2010 for treatment of type 2 diabetes, a disease in which insulin resistance and β-cell dysfunction lead to hyperglycemia. As islet function is lost, the severity of insulin resistance increases. The introduction of DPP-4 inhibitors has brought a novel class of insulinotropic agents for the treatment options available to type 2 diabetic patients. The therapeutic potential of glucagon-like peptide 1 (GLP-1), an incretin peptide, for the treatment of type 2 diabetes was realized in the 1990s. The insulinotropic effects of GLP-1 depend closely on glucose concentrations providing the possibility of glucose normalization without the risk of hypoglycemia. GLP-1 has other non-insulinotropic physiological actions that are advantageous. It suppresses glucagon secretion from a cells and slows gastric emptying, which contributes to satiety and to a slower passage and reabsorption of carbohydrates. GLP-1 also contributes to satiety via a central mechanism as a neurotransmitter with effects on the hypothalamus.

Chemical Properties

White Solid

Originator

Syrrx Inc. (now Takeda San Diego) (Japan)

Uses

Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). Antidiabetic agent.

Definition

ChEBI: A piperidine that is 3-methyl-2,4-dioxo-3,4-dihydropyrimidine carrying additional 2-cyanobenzyl and 3-aminopiperidin-1-yl groups at positions 1 and 2 respectively (the R-enantiomer). Used in the form of its benzoate salt for treatment of t pe 2 diabetes.

brand name

Nesina

Clinical Use

Dipeptidyl peptidase 4 inhibitor:
Treatment of type 2 diabetes in combination with other therapies

Synthesis

To the reaction flask was added 160.0 g (0.36 mol) of alogliptin precursor (III) and 2 L of methanol and stirred until complete dissolution. Subsequently, 46.0 g of trifluoroacetic acid was added and the reaction mixture was stirred at 65 °C for 7 h. The reaction was monitored by TLC until completion. After completion of the reaction, the reaction solution was slowly added dropwise to 2 L of water under stirring and stirring was continued for 30 minutes. The precipitate was collected by filtration and the filter cake was mixed with saturated sodium bicarbonate solution and stirred for 30 minutes to neutralize. The filter was again filtered and the filter cake was washed with water. Finally, recrystallization was carried out using a mixed isopropanol-ethanol solvent to give a white solid product. The product was dried under vacuum at 60 °C for 12 h to give 102.5 g of (R)-2-((6-(3-aminopiperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrile in 83% yield, 98.9% purity, and a melting point of 126~128 °C.

target

DPP-4

Metabolism

Alogliptin does not undergo extensive metabolism. Two minor metabolites were detected following administration of an oral dose of [14C]-alogliptin, N-demethylated alogliptin, M-I (<1% of the parent compound), and N-acetylated alogliptin, M-II (<6% of the parent compound). M-I is an active metabolite and is a highly selective inhibitor of DPP-4 similar to alogliptin; M-II does not display any inhibitory activity towards DPP-4 or other DPP-related enzymes. In vitro data indicate that CYP2D6 and CYP3A4 contribute to the limited metabolism of alogliptin.

References

[1] Patent: CN104086527, 2016, B. Location in patent: Paragraph 0052; 0061-0063; 0074
[2] Patent: CN105777709, 2016, A. Location in patent: Paragraph 0069; 0070
[3] Patent: CN106336396, 2017, A. Location in patent: Paragraph 0013-0119
[4] Patent: WO2015/92807, 2015, A1. Location in patent: Sheet 8
[5] Patent: CN103910710, 2017, B. Location in patent: Paragraph 0064-0065

ALOGLIPTIN(ALOGLIPTINE, ALOGLIPTINA)(850649-61-5)Related Product Information

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