Nateglinide

Base Information

• Chemical Name: Nateglinide
• CAS No.: 105816-04-4
• Molecular Formula: C19H27NO3
• Molecular Weight: 317.428
• Hs Code.: 29242990
• UNII: 41X3PWK4O2,XTM4DQP5S5
• DSSTox Substance ID: DTXSID9040687
• Nikkaji Number: J1.887.176I,J259.863I
• Wikipedia: Nateglinide
• Wikidata: Q2254797,Q27166439
• NCI Thesaurus Code: C61858
• RXCUI: 274332
• Pharos Ligand ID: XXMQZVBR5RUJ
• ChEMBL ID: CHEMBL783,CHEMBL2114389
• Mol file: 105816-04-4.mol

Synonyms:A 4166;A-4166;A4166;AY 4166;AY-4166;AY4166;DJN 608;Fastic;N-((4-isopropylcyclohexyl)carbonyl)phenylalanine;nate-glinide;nateglinide;nateglinide, (cis,D-Phe)-isomer;nateglinide, (D-Phe)-isomer;senaglinide;Starlix;Starsis

Chemical Property of Nateglinide

Chemical Property:

• Appearance/Colour: white crystalline powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 137-141 °C
• Refractive Index: 1.536
• Boiling Point: 527.6 °C at 760 mmHg
• PKA: 3.61±0.10(Predicted)
• Flash Point: 272.9 °C
• PSA: 66.40000
• Density: 1.104 g/cm³
• LogP: 3.65180
• Storage Temp.: Room temp
• Solubility.: DMSO: >5mg/mL
• XLogP3: 3.2
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 6
• Exact Mass: 317.19909372
• Heavy Atom Count: 23
• Complexity: 393

Purity/Quality:

98%99% ^*data from raw suppliers

Nateglinide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 24/25-36

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antidiabetic Agents
• Canonical SMILES: CC(C)C1CCC(CC1)C(=O)NC(CC2=CC=CC=C2)C(=O)O
• Isomeric SMILES: CC(C)C1CCC(CC1)C(=O)N[C@H](CC2=CC=CC=C2)C(=O)O
• Recent ClinicalTrials: A Study to Assess Safety and Efficacy of ASP1941 in Combination With Nateglinide in Type 2 Diabetic Patients
• Recent EU Clinical Trials: Pragmatic Randomised 104 Week Multicentre Trial to Evaluate the Comparative Effectiveness of dapagliflozin and Standard of Care in Type 2 Diabetes. The DECIDE Study.
• Recent NIPH Clinical Trials: Comparison of effect on inflammation and Oxidative stress with Vildagliptin , Nateglinide versus Glimepiride
• Uses: It is used for the treatment of diabetes An Amino-acid derivative that stimulates insulin secretion. Used as an antidiabetic antidiabetic KATP channel blocker An amino-acid derivative that stimulates insulin secretion. Used as an antidiabetic.
• Description: 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.
• Clinical Use: Treatment of type 2 diabetes in combination with metformin
• Drug interactions: 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.

Technology Process of Nateglinide

There total 18 articles about Nateglinide 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: 80.8%

N-<(trans-4-Isopropylcyclohexyl)carbonyl>-D-phenylalanine methyl ester (105746-47-2) → nateglinide (105816-04-4,105816-05-5)

Guidance literature:

N-<(trans-4-Isopropylcyclohexyl)carbonyl>-D-phenylalanine methyl ester; With water; sodium hydroxide; In methanol; at 25 - 30 ℃; for 5h;

With hydrogenchloride; In water; pH=2.0 - 2.5;

Reference yield: 80.0%

trans-4-isopropylcyclohexane-1-carboxylic acid (7077-05-6) + D-(R)-phenylalanine (673-06-3,25191-15-5,658-69-5,67675-33-6) + chloroformic acid ethyl ester (541-41-3) → N-(ethoxycarbonyl)-(D)-phenylalanine (21488-23-3) + nateglinide (105816-04-4,105816-05-5) + 2-[2-[(trans-4-isopropylcyclohexanecarbonyl)amino]-3-phenylpropionylamino]-3-phenylpropionic acid (944746-48-9)

Guidance literature:

trans-4-isopropylcyclohexane-1-carboxylic acid; chloroformic acid ethyl ester; With triethylamine; In acetone; at -10 - -5 ℃; for 1.25h;

D-(R)-phenylalanine; With 4-methyl-morpholine; triethylamine; In water; acetone; at -10 - -5 ℃;

DOI:10.1080/00304940409356630

Reference yield: 75.0%

C17H24O4S (1245809-48-6) + D-(R)-phenylalanine (673-06-3,25191-15-5,658-69-5,67675-33-6) → nateglinide (105816-04-4,105816-05-5)

Guidance literature:

In dichloromethane; at 25 - 30 ℃; for 18.5h;

upstream raw materials:

N-<(trans-4-Isopropylcyclohexyl)carbonyl>-D-phenylalanine methyl ester

trans-4-isopropylcyclohexane-1-carboxylic acid

D-(R)-phenylalanine

chloroformic acid ethyl ester

Downstream raw materials:

ethyl ((1r,4R)-4-isopropylcyclohexane-1-carbonyl)-D-phenylalaninate

N-<(trans-4-Isopropylcyclohexyl)carbonyl>-D-phenylalanine methyl ester

Refernces

• 1、 -. "A high-purity process for the preparation of nateglinide". Paragraph 0028; 0030-0032. . Retrieved 2017/05/04.
• 2、 -. "A PROCESS FOR THE PREPARATION OF N-[[TRANS-4-(1-METHYLETHYL)CYCLOHEXYL]CARBONYL]-D-PHENYLALANINE". Page/Page column 17-18. . Retrieved 2010/10/03.