Domperidone

Base Information

• Chemical Name: Domperidone
• CAS No.: 57808-66-9
• Molecular Formula: C22 H24 Cl N5 O2
• Molecular Weight: 425.918
• Hs Code.: 29333990
• European Community (EC) Number: 260-968-7
• NSC Number: 759575,299589
• UNII: 5587267Z69
• DSSTox Substance ID: DTXSID1045116
• Nikkaji Number: J3.199B
• Wikipedia: Domperidone
• Wikidata: Q424238
• NCI Thesaurus Code: C454
• Pharos Ligand ID: RKD345L4AAUT
• Metabolomics Workbench ID: 43401
• ChEMBL ID: CHEMBL219916
• Mol file: 57808-66-9.mol

Synonyms:Apo Domperidone;Apo-Domperidone;Domidon;Domperidon;Domperidon AL;Domperidon Hexal;Domperidon Stada;Domperidon TEVA;Domperidon-TEVA;Domperidona Gamir;Domperidone;Domperidone Maleate;Domperidone Maleate (1:1);Domperidone Monohydrochloride;Gamir, Domperidona;Gastrocure;Hexal, Domperidon;Maleate, Domperidone;Monohydrochloride, Domperidone;Motilium;Nauzelin;Novo Domperidone;Novo-Domperidone;Nu Domperidone;Nu-Domperidone;Péridys;PMS Domperidone;PMS-Domperidone;R-33,812;R-33812;R33,812;R33812;ratio Domperidone;ratio-Domperidone;Stada, Domperidon

Chemical Property of Domperidone

Chemical Property:

• Appearance/Colour: white powder
• Melting Point: 242.5oC
• Refractive Index: 1.5400 (estimate)
• PKA: pKa 7.90 (Uncertain)
• PSA: 78.82000
• Density: 1.341 g/cm³
• LogP: 3.29110
• Storage Temp.: Store at RT
• Solubility.: DMSO: >10 mg/mL
• Water Solubility.: Slightly soluble in water.
• XLogP3: 3.9
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 5
• Exact Mass: 425.1618527
• Heavy Atom Count: 30
• Complexity: 655

Purity/Quality:

99%min ^*data from raw suppliers

Domperidone ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 62-63
• Safety Statements: 26-36

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CN(CCC1N2C3=C(C=C(C=C3)Cl)NC2=O)CCCN4C5=CC=CC=C5NC4=O
• Recent ClinicalTrials: Treatment Use of Domperidone for Gastroparesis
• Recent EU Clinical Trials: Safety, tolerability and efficacy of nocturnal hypertension treatment with domperidone in the sleep apnea-hypopnea syndrome. Pilot study.
• Recent NIPH Clinical Trials: Impact of varenicline on gastric emptying and effect of domperidone in healthy adults
• Uses: It is a kind of potent peripheral dopamine receptor antagonist with anti-vomiting and gastro-kinetic effects. It can affect the gastrointestinal motility to make the motility and tension of upper gastrointestinal tract return to normal and promote gastric emptying, enhancing the antral and duodenal motility, and coordinating the pyloric contraction. It can be used for the treatment of dyspepsia, and the nausea and vomiting induced by functional, organic, infection, dietary, radiation therapy or drug therapy. Because it almost has no inhibitory effect on dopamine receptor, there are no psychiatric and neurological side effects. And it can be used for treating the nausea caused by treating the Parkinson’s disease through taking dopamine agonists. It can be used as anticholinergic antispasmodics. Domperidone is a kind of phenyl imidazole compounds with a strong role in promoting gastric motility and antiemetic effect. It can strengthen the tension of the sphincter of the lower part of the esophagus, preventing the stomach-esophageal reflux, enhancing the gastric motility, promoting the gastric emptying, coordinating the stomach and duodenal motility, suppressing nausea, vomiting, and effectively preventing the bile reflux without affecting the secretion of gastric juice. This product is a kind of peripheral dopamine receptor antagonists which can directly block the gastrointestinal dopamine receptors and exhibit the stimulating effect of gastric motility. It can enhance the esophageal peristalsis and the tension of esophageal sphincter. Because of its poor penetration through the blood brain barrier, it has almost no antagonism against the dopamine receptor of the brain, and therefore can excluding the side effects of the spirit and the central nervous system. COX2 inhibitor, antiinflammatory, antiarthritic A novel peripheral dopamine receptor antagonist that does not cross the blood-brain barrier; anti-emetic. Domperidone(Motilium) is a dopamine blocker and an antidopaminergic reagent. For management of dyspepsia, heartburn, epigastric pain, nausea, and vomiting.
• Production method: 2-nitro-1, 4-dichlorobenzene is reacted with 4-amino-cyclohexanecarboxylic acid ethyl ester and is further subject to hydrogenation reduction, urea cyclization, hydrolysis, to give 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-benzimidazol-2-ketone. Hydroxyl propylamine can have nucleophilic substitution of the chlorine of 2-nitro-chlorobenzene and then be subject to hydrogenation to reduce the nitro group to amino group; then have cyclization with potassium chloride and further chlorination to give 1-(3-chloropropyl)-2,3-dihydro-1H-benzimidazol-2-ketone. The two benzimidazole derivative obtained above are processed as follows and can give domperidone. 2.3 parts of 1-(3-chloropropyl)-2,3-dihydro-1H-benzimidazol-2-ketone, 2.5 parts of 5--chloro-I-(piperidin-4-yl)-1,3-2H-dihydro-benzimidazol-2-one, 3.2 parts of sodium carbonate, 0.1 parts of potassium iodide and 80 parts of 4-methyl-2-pentanone were stirred and reflux for 24h. After being cooled to room temperature, add water, filter off the insolubles and purify it by silica gel column chromatography with the eluting solution being chloroform and 10% methanol mixture. The effluent containing the product were collected and concentrated. The residue was crystallized using 4-methyl-2-pentanone. After filtration, apply re-crystallization with the mixture of dimethylformamide and water to obtain 1.3 parts of domperidone with the yield being 30% and the mp being 242.5 ℃.
• Therapeutic Function: Antiemetic
• Clinical Use: Acute nausea and vomiting (including that caused by levodopa and bromocriptine)Gastro-oesophageal refluxDyspepsia
• Drug interactions: Potentially hazardous interactions with other drugsAntibacterials: possible increased risk of ventricular arrhythmias with clarithromycin, delamanid and erythromycin - avoid with clarithromycin and erythromycin.Antifungals: possibly increased risk of ventricular arrhythmias with itraconazole, ketoconazole and voriconazole - avoid.Antimalarials: possible increased risk of ventricular arrhythmias with piperaquine with artenimol - avoid.Antivirals: possible increased risk of ventricular arrhythmias with boceprevir; possible increased risk of ventricular arrhythmias with ritonavir, saquinavir and telaprevir - avoidApomorphine: possible increased risk of ventricular arrhythmias.Cobicistat: possible increased risk of ventricular arrhythmias - avoid.Cytotoxics: increased risk of ventricular arrhythmias with bosutinib and ceritinib - avoid with bosutinib.

Technology Process of Domperidone

There total 3 articles about Domperidone 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: 51.0%

1-(3-aminopropyl)benzimidazol-2-one (64928-87-6) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → domperidone (57808-66-9)

Guidance literature:

With sodium bromide; sodium sulfite; In nitromethane; for 32h; Solvent; Concentration; Reflux;

Reference yield:

chloroform (67-66-3,8013-54-5) + 4-methyl-2-pentanone (108-10-1) + 1-(3-Chloropropyl)-1,3-dihydrobenzoimidazol-2-one (62780-89-6) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → domperidone (57808-66-9)

Guidance literature:

With potassium iodide; sodium carbonate; In water;

Reference yield:

→ domperidone (57808-66-9)

Guidance literature:

upstream raw materials:

chloroform

4-methyl-2-pentanone

1-(3-Chloropropyl)-1,3-dihydrobenzoimidazol-2-one

5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

Refernces

• 1、 -. "1,3-Dihydro-1-[3-(1-piperidinyl)propyl]-2H-benzimidazol-2-ones and related compounds". . . Retrieved 2008/06/13.