565453-40-9

Basic information

• Product Name: VILDAGLIPTIN
• Synonyms: Vildagliptin Carboxylic Acid Metabolite;(2S)-1-[2-[(3-hydroxy-1-adamantyl)amino]acetyl]pyrrolidine-2-carboxylic acid;Vildagliptin Carboxy Acid;N-(3-Hydroxytricyclo[3.3.1.1(3,7)]dec-1-yl)glycyl-L-proline
• CAS NO: 565453-40-9
• Molecular Formula: C17H25N3O2
• Molecular Weight: 303.4
• Product Categories: Chiral Reagents;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 565453-40-9.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 556.412°C at 760 mmHg
• Flash Point: 290.308°C
• Appearance: /
• Density: 1.349g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.615
• PKA: 3.18±0.20(Predicted)
• CAS DataBase Reference: VILDAGLIPTIN(CAS DataBase Reference)
• NIST Chemistry Reference: VILDAGLIPTIN(565453-40-9)
• EPA Substance Registry System: VILDAGLIPTIN(565453-40-9)

Safety Data

• Hazardous Substances Data: 565453-40-9(Hazardous Substances Data)

Usage

Uses

N-(3-Hydroxytricyclo[3.3.1.13,7]dec-1-yl)glycyl-L-proline, is a metabolite of Vildagliptin (V305000), a class of oral anti-hyperglycemic agents that inhibit dipeptidyl peptidase 4 (DPP-4), which can act as a serine exopeptidase.

InChI:InChI=1/C17H26N2O4/c20-14(19-3-1-2-13(19)15(21)22)9-18-16-5-11-4-12(6-16)8-17(23,7-11)10-16/h11-13,18,23H,1-10H2,(H,21,22)/t11?,12?,13-,16?,17?/m0/s1

Upstream product

• 702-82-9 3-aminoadamantan-1-ol 
• 23500-10-9 (S)-1-(2-chloroacetyl)pyrrolidine-2-carboxylic acid 
• 147-85-3 L-proline 
• 274901-16-5 vildagliptin 

Relevant articles and documents

Dipeptidyl peptidase-4 greatly contributes to the hydrolysis of vildagliptin in human liver

The major metabolic pathway of vildagliptin in mice, rats, dogs, and humans is hydrolysis at the cyano group to produce a carboxylic acid metabolite M20.7 (LAY151), whereas the major metabolic enzyme of vildagliptin has not been identified. In the present study, we determined the contribution rate of dipeptidyl peptidase-4 (DPP-4) to the hydrolysis of vildagliptin in the liver. We performed hydrolysis assay of the cyano group of vildagliptin using mouse, rat, and human liver samples. Additionally, DPP-4 activities in each liver sample were assessed by DPP-4 activity assay using the synthetic substrate H-glycyl-prolyl-7-amino-4-methylcoumarin (Gly-Pro-AMC). M20.7 formation rates in liver microsomes were higher than those in liver cytosol. M20.7 formation rate was significantly positively correlated with the DPP-4 activity using Gly-Pro-AMC in liver samples (r = 0.917, P 0.01). The formation of M20.7 in mouse, rat, and human liver S9 fraction was inhibited by sitagliptin, a selective DPP-4 inhibitor. These findings indicate that DPP-4 is greatly involved in vildagliptin hydrolysis in the liver. Additionally, we established stable single expression systems of human DPP-4 and its R623Q mutant, which is the nonsynonymous single-nucleotide polymorphism of human DPP-4, in human embryonic kidney 293 (HEK293) cells to investigate the effect of R623Q mutant on vildagliptin-hydrolyzing activity. M20.7 formation rate in HEK293 cells expressing human DPP-4 was significantly higher than that in control HEK293 cells. Interestingly, R623Q mutation resulted in a decrease of the vildagliptin-hydrolyzing activity. Our findings might be useful for the prediction of interin-dividual variability in vildagliptin pharmacokinetics.

Preparation process of vildagliptin impurity

The invention discloses a preparation process of a vildagliptin impurity, namely 2-(3-hydroxy adamantane-1-yl) hexahydropyrrole [1, 2-a] piperazine-1, 4-diketone. According to the process, L-proline is used as an initial raw material, and 2-(3-hydroxy adamantane- 1-yl) hexahydropyrrole [1, 2-a] piperazine-1, 4-diketone is prepared through secondary N-chloracetylation reaction, amino substitution and intramolecular cyclization. The method is mainly characterized in that reaction steps and time are shortened, and expensive catalysts and tedious operation means are not involved in the whole reaction process. The preparation process has the advantages of easily available raw materials, mild and easily controllable reaction conditions and high product purity, and the vildagliptin impurity can be used as a reference substance for vildagliptin bulk drug quality control.