Rebamipide

Base Information

• Chemical Name: Rebamipide
• CAS No.: 90098-04-7
• Deprecated CAS: 111911-87-6,139344-42-6
• Molecular Formula: C19H15ClN2O4
• Molecular Weight: 370.792
• Hs Code.: 29337900
• European Community (EC) Number: 815-380-0
• NSC Number: 758955
• UNII: LR583V32ZR
• DSSTox Substance ID: DTXSID8045937
• Nikkaji Number: J227.452C
• Wikipedia: Rebamipide
• Wikidata: Q7301602
• NCI Thesaurus Code: C29852
• Pharos Ligand ID: WWXB6USS1Y2J
• Metabolomics Workbench ID: 152776
• ChEMBL ID: CHEMBL1697771
• Mol file: 90098-04-7.mol

Synonyms:2-(4-chlorobenzoylamino)-3-(2(1H)-quinolinon-4-yl)propionic acid;OPC 12759;OPC-12759;rebamipide;rebamipide, (+)-isomer;rebamipide, (-)-isomer

Chemical Property of Rebamipide

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 2.83E-20mmHg at 25°C
• Melting Point: 288-290 °C dec.
• Refractive Index: 1.634
• Boiling Point: 695 °C at 760 mmHg
• PKA: 3.38±0.10(Predicted)
• Flash Point: 374.1 °C
• PSA: 99.26000
• Density: 1.394 g/cm³
• LogP: 2.99810
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: >5mg/mL
• XLogP3: 2.4
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 5
• Exact Mass: 370.0720347
• Heavy Atom Count: 26
• Complexity: 598

Purity/Quality:

99% ^*data from raw suppliers

Rebamipide ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: C1=CC=C2C(=C1)C(=CC(=O)N2)CC(C(=O)O)NC(=O)C3=CC=C(C=C3)Cl
• Recent ClinicalTrials: Clinical Study to Investigate the Pharmacokinetics and Safety/Tolerability of SA001 in Healthy Male Volunteers
• Recent NIPH Clinical Trials: Keratoconjunctivitis after cataract surgery and protective effect of rebamipide ocular solution.
• Description: Rebamipide is a quinolinone derivative that stimulates endogenous PGE2 generation in gastric mucosa, enhancing gastric mucosal defense in a COX-2-dependent manner. Rebamipide has been shown to inhibit the production of reactive oxygen species and to decrease cytokine release induced by H. pylori infection. A daily oral dose of 100 mg/kg was found to be protective against the development of pyloric channel ulcers in Mongolian gerbils infected with H. pylori. In addition to the stomach, rebamipide can also enhance secretion of mucin covering the conjunctiva and cornea, which is important for tear film adhesion. Rebamipide, a gastroprotective drug, was developed in Japan and was proven to be superior to cetraxate, the former most prescribed drug of the same category, in 1989 in the treatment for gastric ulcers. The initially discovered basic mechanisms of action of rebamipide included its action as a prostaglandin inducer and oxygen free-radical scavenger. In the last 5 years, several basic and clinical studies have been performed for functional dyspepsia, chronic gastritis, NSAID-induced gastrointestinal injuries, gastric ulcer following eradication therapy for Helicobacter pylori, gastric ulcer after endoscopic surgery and ulcerative colitis. In addition, several molecules have been identified as therapeutic targets of rebamipide to explain its pleiotropic pharmacological actions.
• Indications: 1. Prevents and treatment of injury of gastric mucosal caused by NSAIDs Rebamipide has an obvious reversal effect on the side effects of NSAIDs drug-induced reduction of the synthesis of gastric mucosal prostaglandin and increased permeability of mucosa. Further study has found that patients taking NSAIDs had gotten high expression of gastric epithelial HIF-1, suggesting that the gastric mucosa of patients is within hypoxic-ischemic state; However, patients taking rebamipide has significantly reduced HIF-1 expression, demonstrating that rebamipide has a very good protective effect on the gastric mucosa of patients taking NSAIDs table. From this perspective, rebamipide may have a prevention and treatment effect on NSAIDs (especially non-selective NSAIDs) induced gastric mucosal damage. 2. HP-related gastritis treatment Haruma et al have reported that: in the observation of clinical treatment of 86 HP-positive patients, 53 patients taking rebamipide had stomach antrum and stomach body monocytes with significant reduction on granulocytes cell infiltration and had the stomach inflammation much more be alleviated than those without medication, indicating that it has a high-quality effect on treating HP-associated gastritis. 3. Other Studies have reported that patients with gastric cancer who have taken rebamipide before surgeries had significant lower body temperature than the control group at 3 days after surgeries. Moreover, their serum IL-6 levels are also significantly lower than the control group, demonstrating that rebamipide has alleviated effect on the post-surgery systemic inflammatory response syndrome of gastric cancer patients; rebamipide may also become a new means of treatment for ulcerative colitis; may also become a new and effective approach for treating Meniere's disease.
• Uses: It is used for treating stomach ulcers. It is a kind of novel anti-ulcer drugs. Shows antiulcer activity in rats antiulcer, antioxidant An inducer of endogenous prostaglandin and a oxygen-derived free radical scavenger.

Technology Process of Rebamipide

There total 23 articles about Rebamipide 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: 96.9%

2-amino-3-[2(1H)-quinolinone-4-yl]propionic acid dihydrochloride dihydrate (914769-50-9) + 4-chloro-benzoyl chloride (122-01-0) → rebamipide (90098-04-7,111911-87-6)

Guidance literature:

2-amino-3-[2(1H)-quinolinone-4-yl]propionic acid dihydrochloride dihydrate; 4-chloro-benzoyl chloride; With sodium hydroxide; In water; acetone; at 0 ℃;

With hydrogenchloride; In water; acetone;

Reference yield: 96.2%

2-amino-3-[6-bromo-2(1H)-quinolon-4-yl]propionic acid (889573-80-2) + 4-chloro-benzoyl chloride (122-01-0) + 2-amino-3-<2-(1H)-quinolinon-4-yl>propionic acid hydrochloride (4876-14-6,132210-24-3) → rebamipide (90098-04-7,111911-87-6)

Guidance literature:

2-amino-3-[6-bromo-2(1H)-quinolon-4-yl]propionic acid; 2-amino-3-<2-(1H)-quinolinon-4-yl>propionic acid hydrochloride; With sodium hydroxide; hydrogen; Raney nikel; In water; at 20 ℃; for 2h;

4-chloro-benzoyl chloride; With sodium hydroxide; In water; acetone; at 0 ℃;

With hydrogenchloride; In water; acetone;

Reference yield: 94.0%

ethyl 2-(4-chlorobenzamido)-2-ethoxyoxo-3-[2-(1H)-quinolin-4-yl]propionate (1028268-32-7) → rebamipide (90098-04-7,111911-87-6)

Guidance literature:

With water; sodium hydroxide; In ethanol; Reflux;

upstream raw materials:

4-chloro-benzoyl chloride

2-amino-3-<2-(1H)-quinolinon-4-yl>propionic acid hydrochloride

4-bromomethyl-2(1H)-quinolinone

2-acetylamino-2-(ethoxycarbonyl)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionic acid ethyl ester

Downstream raw materials:

2-(4-chlorobenzoylamino)-3-(2-quinolon-4-yl)propionic acid tris(hydroxymethyl)aminomethane salt

2-(4-chlorobenzoylamino)-3-(2-quinolon-4-yl)propionic acid L-arginine salt

2-(4-chlorobenzoylamino)-3-(2-quinolon-4-yl)propionic acid diethanolamine salt

2-(4-chlorobenzoylamino)-3-(2-quinolon-4-yl)propionic acid L-lysine salt

Refernces

• 1、 -. "New process for synthesizing rebamipide". . . Retrieved 2020/12/30.
• 2、 Babu, Prashanth Kumar,Bodireddy, Mohan Reddy,Puttaraju, Reshma Choudlu,Vagare, Dnyaneshwar,Nimmakayala, Raghu,Surineni, Naresh,Gajula, Madhusudana Rao,Kumar, Pramod. "Magic Bullet! Rebamipide, a Superior Anti-ulcer and Ophthalmic Drug and Its Large-Scale Synthesis in a Single Organic Solvent via Process Intensification Using Krapcho Decarboxylation". . p. 773 - 779. Retrieved 2018/06/11.