(S)-1-[2-((5S,7S)-3-hydroxy-adamantan-1-ylamino)-acetyl]-pyrrolidine-2-carbonitrile

Base Information

• Chemical Name: (S)-1-[2-((5S,7S)-3-hydroxy-adamantan-1-ylamino)-acetyl]-pyrrolidine-2-carbonitrile
• CAS No.: 274901-16-5
• Molecular Formula: C17H25N3O2
• Molecular Weight: 303.404
• Hs Code.: 29339900
• European Community (EC) Number: 630-410-0
• Nikkaji Number: J2.160.644H
• Wikipedia: Vildagliptin
• Wikidata: Q27462467
• Pharos Ligand ID: MH3S1PUVAHKH
• ChEMBL ID: CHEMBL3084811
• Mol file: 274901-16-5.mol

Synonyms:274901-16-5;(S)-1-[2-((5S,7S)-3-hydroxy-adamantan-1-ylamino)-acetyl]-pyrrolidine-2-carbonitrile;(2S)-1-((3-hydroxyadamantan-1-yl)glycyl)pyrrolidine-2-carbonitrile;(2S)-1-[2-[[(5S,7R)-3-hydroxy-1-adamantyl]amino]acetyl]pyrrolidine-2-carbonitrile;(S)-1-(((1r,3R,5R,7S)-3-hydroxyadamantan-1-yl)glycyl)pyrrolidine-2-carbonitrile;1044676-63-2;Vildagliptin/metformin;D0R9HL;CHEMBL319819;CHEMBL3084811;SCHEMBL10031674;SCHEMBL16153676;SCHEMBL16155482;(S)-1-(2-(((1r,3R,5R,7S)-3-hydroxyadamantan-1-yl)amino)acetyl)pyrrolidine-2-carbonitrile;LAF237;NVP-LAF 237;BDBM123776;(2S)-1-[2-[(3-Hydroxy-tricyclo[3.3.1.13,7 ]dec-1-yl)amino]acetyl]-2-pyrrolidinecarbonitrile;BDBM50129889;FD6071;MFCD08275142;AKOS015924571;BS-1016;CS-O-10170;Q-101364;Q27462467;Z1741976872;1-[2-(3-Hydroxy-adamantan-1-ylamino)-acetyl]-pyrrolidine-2-carbonitrile;(2S)-1-(2-{[(1r,3s,5R,7S)-3-hydroxyadamantan-1- yl]amino}acetyl)pyrrolidine-2-carbonitrile (11);(2s)-1-{n-[(1r,3s,5r,7s)-3-Hydroxytricyclo[3.3.1.1~3,7~]dec-1-Yl]glycyl}pyrrolidine-2-Carbonitrile

Chemical Property of (S)-1-[2-((5S,7S)-3-hydroxy-adamantan-1-ylamino)-acetyl]-pyrrolidine-2-carbonitrile

Chemical Property:

• Appearance/Colour: white crystalline powder
• Melting Point: 153-155?C
• Boiling Point: 531.3 °C at 760 mmHg
• PKA: 15.05±0.40(Predicted)
• Flash Point: 275.1 °C
• PSA: 76.36000
• Density: 1.27 g/cm³
• LogP: 1.50308
• Storage Temp.: -20°C Freezer
• Solubility.: Soluble in DMSO (up to 45 mg/ml), in DMF (up to 20 mg/ml), or in Ethanol (up to 20 mg/ml).
• XLogP3: 0.9
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 3
• Exact Mass: 303.19467705
• Heavy Atom Count: 22
• Complexity: 523

Purity/Quality:

99%min ^*data from raw suppliers

Vildagliptin ^*data from reagent suppliers

Safty Information:

• Statements: 28-38-41-48
• Safety Statements: 24/25-26-28-36/37/39

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CC(N(C1)C(=O)CNC23CC4CC(C2)CC(C4)(C3)O)C#N
• Isomeric SMILES: C1C[C@H](N(C1)C(=O)CNC23C[C@H]4C[C@@H](C2)CC(C4)(C3)O)C#N
• Recent ClinicalTrials: Efficacy and Safety of Combination Therapy of Vildagliptin/Metformin in Patients in Type 2 Diabetes Mellitus (T2DM)
• Recent EU Clinical Trials: A prospective, multicenter, randomized, open-label study of 12 week duration to evaluate the effect of VILDagliptin added to insulin on glycaemic control in haemoDIALyzed patients with type 2 diabetes: probe analysis of CGM
• Recent NIPH Clinical Trials: Randomized prospective study to investigate the association between intestinal FDG accumulation obtained using 18F-FDG-PET/MRI and various parameters in patients taking metformin or vildagliptin
• Uses: Glyptins are class of oral anti-hyperglycemic agents that inhibit dipeptidyl peptidase 4 (DPP-4), which can act as a serine exopeptidase. Aside from their use in type 2 diabetes, gliptins have positive cardiovascular and anti-inflammtatory effects. Antidiabetic. Vildagliptin (LAF-237) inhibits DPP?4 with IC50 of 2.3 nM The major metabolite of Vildagliptin
• Description: Vildagliptin, a DPP-4 inhibitor, was launched for the oral treatment of type 2 diabetes. Vildagliptin is the second DPP-4 inhibitor to reach the market behind sitagliptin, which was introduced in 2006. DPP-4 inhibitors act by slowing the inactivation of incretins, which are endogenous peptides involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase the synthesis and release of insulin from pancreatic βcells via intracellular signaling pathways involving cAMP. GLP-1 also lowers glucagon secretion from pancreatic α cells, which leads to reduced hepatic glucose production. However, although GLP-1 and GIP effectively lower blood glucose, they are short-lived as a result of rapid inactivation by the ubiquitous serine protease DPP-4. By inhibiting DPP-4, vildagliptin increases the concentration and duration of active incretin levels, which in turn results in increased insulin release and decreased glucagon levels in a glucose-dependent manner. Both vildagliptin and sitagliptin are potent, competitive, reversible inhibitors of DPP- 4 (IC50=3.5 and 18 nM, respectively), and they both show slow, tight-binding inhibition kinetics.
• Clinical Use: Dipeptidyl peptidase 4 inhibitor: Treatment of type 2 diabetes mellitus in combination with other antidiabetic drugs
• Drug interactions: Potentially hazardous interactions with other drugs None known

Technology Process of (S)-1-[2-((5S,7S)-3-hydroxy-adamantan-1-ylamino)-acetyl]-pyrrolidine-2-carbonitrile

There total 52 articles about (S)-1-[2-((5S,7S)-3-hydroxy-adamantan-1-ylamino)-acetyl]-pyrrolidine-2-carbonitrile which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 95.0%

1-[2-(3-hydroxyadamant-1-yl-amino)acetyl]pyrrolidin-(2S)-carbonitrile calcium(II)-chloride → vildagliptin (274901-16-5,1044676-63-2)

Guidance literature:

With sodium carbonate; sodium chloride; In dichloromethane; at 20 - 40 ℃; Product distribution / selectivity;

Reference yield: 91.9%

(2S)‐1‐[[(3-hydroxytricyclo[3.3.1.1[3,7]]decane-1-yl)imino]acetyl]pyrrolidine-2-carbonitrile → vildagliptin (274901-16-5,1044676-63-2)

Guidance literature:

With palladium on activated charcoal; ammonium formate; In tetrahydrofuran; at 20 ℃; for 8h; Reagent/catalyst; Solvent; Temperature;

Reference yield: 90.8%

[(3‐hydroxytricyclo[3.3.1.13,7]decan‐1‐yl)amino]acetic acid (1032564-18-3) + (S)-pyrrolidine-2-carbonitrile p-toluenesulfonate → vildagliptin (274901-16-5,1044676-63-2)

Guidance literature:

(S)-pyrrolidine-2-carbonitrile p-toluenesulfonate; With sodium hydroxide; In dichloromethane; at 0 ℃; for 1.5h;

[(3‐hydroxytricyclo[3.3.1.13,7]decan‐1‐yl)amino]acetic acid; With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 ℃; Concentration;

upstream raw materials:

3-aminoadamantan-1-ol

(S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile

(S)-1-(2-chloroacetyl) pyrrolidine-2-carboxamide

L-prolinamide

Downstream raw materials:

2-(3-hydroxyadamantan-1-yl)-1-imino-hexahydropyrrolo[1,2-a]pyrazin-4-one

vildagliptin carboxylic acid

Refernces

• 1、 Zhang, Li,Jiang, Lan,Guan, Xiaoshu,Cai, Linhong,Wang, Jingyu,Xiang, Peng,Pan, Junyi,Hu, Xiangnan. "A facile method to synthesize vildagliptin". . p. 305 - 309. Retrieved 2020/12/01.
• 2、 -. "Synthesis method of vildagliptin". Paragraph 0031; 0037; 0038; 0044; 0045; 0051; 0067. . Retrieved 2020/09/12.