Repaglinide

Base Information

• Chemical Name: Repaglinide
• CAS No.: 135062-02-1
• Molecular Formula: C27H36N2O4
• Molecular Weight: 452.594
• Hs Code.: 2933399090
• European Community (EC) Number: 629-921-1
• NSC Number: 759893
• UNII: 668Z8C33LU
• DSSTox Substance ID: DTXSID3023552
• Nikkaji Number: J555.407A
• Wikipedia: Repaglinide
• Wikidata: Q2195995
• NCI Thesaurus Code: C47703
• RXCUI: 73044
• Pharos Ligand ID: TYZKJAMBL4TW
• Metabolomics Workbench ID: 43180
• ChEMBL ID: CHEMBL1272
• Mol file: 135062-02-1.mol

Synonyms:(+)-2-ethoxy-alpha-(((S)-alpha-isobutyl-o-piperidinobenzyl)carbamoyl)-p-toluic acid;(+)-repaglinide;(-)-repaglinide;(S)-2-ethoxy-4-(2-((3-methyl-1-(2-(1-piperidinyl)-phenyl)butyl)amino)-2-oxoethyl)-benzoic acid;2-ethoxy-4-(2-(((1R)-3-methyl-1-(2-(1-piperidinyl)phenyl)butyl)amino)-2-oxoethyl)benzoic acid;2-ethoxy-4-(2-((3-methyl-1-(2-(1-piperidinyl)phenyl)butyl)amino)-2-oxoethyl)benzoic acid;2-ethoxy-N-(alpha-(2-methyl-1-propyl)-2-piperidinobenzyl)-4-carbamoylmethylbenzoic acid;AG-EE 388;AG-EE 388 ZW;AG-EE 623 ZW;AG-EE 624ZW;AG-EE-623-ZW;AG-EE-623ZW;AG-EE-624ZW;AGEE-623ZW;GlucoNorm;NovoNorm;Prandin;repa-glinide;repaglinide;repaglinide impurity E;repaglinide related compound E;repaglinide, (+-)-isomer

Chemical Property of Repaglinide

Chemical Property:

• Appearance/Colour: white to off-white solid
• Vapor Pressure: 5E-19mmHg at 25°C
• Melting Point: 129-130.2 °C
• Refractive Index: 1.567
• Boiling Point: 672.9 °C at 760 mmHg
• PKA: 4.19±0.10(Predicted)
• Flash Point: 360.8 °C
• PSA: 78.87000
• Density: 1.137 g/cm³
• LogP: 5.67580
• Storage Temp.: 2-8°C
• Solubility.: DMSO: 34 mg/mL
• Water Solubility.: 89.99mg/L(25 oC)
• XLogP3: 5.2
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 10
• Exact Mass: 452.26750763
• Heavy Atom Count: 33
• Complexity: 619

Purity/Quality:

99% min ^*data from raw suppliers

Repaglinide ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antidiabetic Agents
• Canonical SMILES: CCOC1=C(C=CC(=C1)CC(=O)NC(CC(C)C)C2=CC=CC=C2N3CCCCC3)C(=O)O
• Isomeric SMILES: CCOC1=C(C=CC(=C1)CC(=O)N[C@@H](CC(C)C)C2=CC=CC=C2N3CCCCC3)C(=O)O
• Recent ClinicalTrials: A Drug Interaction Study of LY3871801 in Healthy Participants
• Recent EU Clinical Trials: Geriatric outcomes among older Type 2 diabetic patients treated with DPP4 inhibitors or glinides: focus on cognitive functioning (GOOD-WP3)
• Recent NIPH Clinical Trials: The Clinical Comparison of Antidiabetic Agents Treating Postprandial Hyperglycemia, between Repaglinide alone and Mitiglide/Voglibose Fixed-dose Combination using Continuous Glucose Monitoring on Postprandial Profiles.
• Uses: 1. Anti-diabetic medicine. Oral non-sulfonylurea hypoglycemic agent, for the treatment of typeⅡdiabetes. 2. Used as hypolycemic agent. Non-sulfonylurea oral hypoglycemic agent. Used as an antidiabetic The R-enantiomer showed only weak hypoglycemic activity. Repaglinide impurity antineoplastic A KIR6 (KATP) channel blocker
• Production method: Convert the compounds (Ⅰ) to their N-acetyl derivatives, with L-glutamate to get salt and then get (S) shaped optical isomer; react with the compounds (Ⅱ) to form amide (Ⅲ) and then hydrolyzed to obtain the product.
• Description: Repaglinide was marketed in the US as an orally active hypoglycemic agent in patients with a type Ⅱ diabetes mellitus, to lower blood glucose in synergistic combination with metformin, when hyperglycemia cannot be controlled by diet, exercise or metformin alone. Chiral (S)-repaglinide can be synthesized in several ways, each involving a stereoselective reduction of an imine or enamine group. Repaglinide is a nonsulfonylurea belonging to the meglitinide family, with an insulin-releasing effect mediated by pancreatic betacells, by closing the ATP-sensitive K+ channels that, in turn, increases the cytosolic concentration of Ca++. In several animal models, repaglinide was more efficient than glibenclamide as a dose-dependant promoter of insulin release, but its mechanism of action is probably slightly different. Repaglinide has a rapid onset of action, a short duration of action and a reduced risk of hypoglycemia compared to glyburide. Repaglinide is a metaglitinide antidiabetic agent that blocks ATP-dependent potassium (Kir6) channels in pancreatic β-cells (Kd = 0.42 nM for the sulphonylurea receptor SUR1 when co-expressed with Kir6.2). In vivo, repaglinide lowers blood glucose in fasted rats and dogs (ED50s = 10 and 28.3 μg/kg, respectively). Formulations containing repaglinide have been used to control blood sugar levels in patients with type 2 diabetes.
• Clinical Use: Repaglinide is a nonsulfonylurea insulin secretagogue that was introduced in the United States in 1998 for type 2 diabetes.
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: effects enhanced by clarithromycin and possibly trimethoprim - avoid with trimethoprim; hypoglycaemic effect antagonised by rifampicin. Antifungals: effect possibly enhanced by itraconazole. Ciclosporin: may increase repaglinide concentration, possibly enhanced hypoglycaemic effect. Clopidogrel: avoid concomitant use if possible due to increased repaglinide exposure. Cytotoxics: avoid with lapatinib. Lipid-lowering agents: increased risk of severe hypoglycaemia with gemfibrozil - avoid.

Technology Process of Repaglinide

There total 49 articles about Repaglinide 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: 96.0%

(S)-(+)-ethyl 2-ethoxy-4-<2-<<3-methyl-1-<2-(1-piperidinyl)phenyl>butyl>amino>-2-oxoethyl>-benzoate (147770-06-7) → (S)-repaglinide (135062-02-1)

Guidance literature:

With ethanol; water; sodium hydroxide; Reflux;

Reference yield: 89.9%

C28H38N2O4 → (S)-repaglinide (135062-02-1)

Guidance literature:

With potassium hydroxide; In acetonitrile; for 6h; Reflux;

Reference yield: 85.1%

C34H42N2O4 → (S)-repaglinide (135062-02-1)

Guidance literature:

With ethanol; sodium hydroxide; for 5h; Reflux;

upstream raw materials:

(S)-(+)-ethyl 2-ethoxy-4-<2-<<3-methyl-1-<2-(1-piperidinyl)phenyl>butyl>amino>-2-oxoethyl>-benzoate

piperidine

2-(piperidin-1-yl)benzonitrile

2-Chlorobenzonitrile

Downstream raw materials:

phosphoric acid salt of (S)-(+)-2-ethoxy-4-{[3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl]-methyl}-benzoic acid

3’-hydroxyrepaglinide

Refernces

• 1、 -. "Synthesis process of hypoglycemic drug repaglinide". Paragraph 0083-0086; 0094-0097. . Retrieved 2020/09/16.
• 2、 Nagarajan, Periyandi,Rajendiran, Chinnapillai,Naidu,Dubey. "Studies on diastereofacial selectivity of a chiral tert-butanesulfinimines for the preparation of (S)-3-Methyl-1-(2-piperidin-1-yl-phenyl)butylamine for the synthesis of repaglinide". . p. 9345 - 9350. Retrieved 2013/11/19.