Cimetidine

Base Information

• Chemical Name: Cimetidine
• CAS No.: 51481-61-9
• Molecular Formula: C10H16N6S
• Molecular Weight: 252.343
• Hs Code.: 29339900
• European Community (EC) Number: 257-232-2
• NSC Number: 757428,335308
• UNII: 80061L1WGD
• DSSTox Substance ID: DTXSID4020329
• Nikkaji Number: J3.190I
• Wikipedia: Cimetidine
• Wikidata: Q409492
• NCI Thesaurus Code: C374
• RXCUI: 2541
• Pharos Ligand ID: 2HM79A95BD25
• Metabolomics Workbench ID: 42845
• ChEMBL ID: CHEMBL30
• Mol file: 51481-61-9.mol

Synonyms:Altramet;Biomet;Biomet400;Cimetidine;Cimetidine HCl;Cimetidine Hydrochloride;Eureceptor;HCl, Cimetidine;Histodil;Hydrochloride, Cimetidine;N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine;SK and F 92334;SK and F-92334;SK and F92334;SKF 92334;SKF-92334;SKF92334;Tagamet

Chemical Property of Cimetidine

Chemical Property:

• Appearance/Colour: white solid
• Melting Point: 139-144 °C
• Refractive Index: 1.5700 (estimate)
• Boiling Point: 488 °C at 760 mmHg
• PKA: pKa 6.80 (Uncertain)
• Flash Point: 248.9 °C
• PSA: 114.19000
• Density: 1.27 g/cm³
• LogP: 1.37918
• Storage Temp.: 2-8°C
• Solubility.: Slightly soluble in water, soluble in ethanol (96 per cent), practically insoluble in methylene chloride. It dissolves in dilute mineral acids.
• Water Solubility.: 0.5 g/100 mL at 20 ºC
• XLogP3: 0.4
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 7
• Exact Mass: 252.11571571
• Heavy Atom Count: 17
• Complexity: 296

Purity/Quality:

99% ^*data from raw suppliers

Cimetidine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,Xn
• Hazard Codes: T,Xn
• Statements: 60-42/43-36/37/38-20/22
• Safety Statements: 53-26-36/37/39-45-36-22

MSDS Files:

SDS file from LookChem

Useful:

• Chemical Classes: Other Uses -> Pharmaceuticals
• Drug Classes: Antiulcer Agents
• Canonical SMILES: CC1=C(N=CN1)CSCCNC(=NC)NC#N
• Recent ClinicalTrials: Pharmacokinetic Drug-Drug Interaction Study to Identify Biomarkers of Kidney Transporters
• Recent EU Clinical Trials: Study on the effects of an OCT2/MATE1 substrate (metformin) and inhibitor (cimetidine) on the exposure of trifluridine/tipiracil (Lonsurf?) in patients with metastatic colorectal cancer (mCRC).
• Recent NIPH Clinical Trials: Open-label crossover exploratory research to elucidate endogenous biomarkers to investigate renal organic cation transporter-mediated drug interactions
• Description: Cimetidine (brand name: Tagamet) is a kind of histamine H2 receptor antagonist being capable of inhibiting the production of stomach acid, which reduces the gastric volume and acidity. It is mainly used for the treatment of heartburn and peptic ulcers. There are also evidences that it can be used for the treatment of common warts, chronic calcific tendinitis of the shoulder, and even colorectal cancer. It is capable of not only inhibiting the gastric acid secretion, as well as pepsin and gastrins output, but also inhibiting the activity of cytochrome P450. It reduces the gastric acid secretion through binding to the H2 receptor locating on the basolateral membrane of the gastric parietal cell, and further blocking histamine effect. Cimetidine is a representative of first-generation antihistamine drugs that block H2 receptors.
• Uses: antibacterial Cimetidine is used for treating ulcer problems of the stomach and duodenum and for other conditions accompanied by an elevation of acidity and excess secretion of gastric juice. It is used for preventing injuries and the blood flow of the upper regions of the gastrointestinal tract.
• Indications: Cimetidine, the first released H2-blocker, like histamine, contains an imidazole ring structure. It is well absorbed following oral administration, with peak blood levels 45 to 90 minutes after drug ingestion. Blood levels remain within therapeutic concentrations for approximately 4 hours after a 300-mg dose. Following oral administration, 50 to 75% of the parent compound is excreted unchanged in the urine; the rest appears primarily as the sulfoxide metabolite.
• Therapeutic Function: Antiulcer
• Clinical Use: H2 antagonist: Conditions associated with hyperacidity Refractory uraemic pruritus (unlicensed use)
• Drug interactions: Potentially hazardous interactions with other drugs Alpha-blockers: effects of tolazoline antagonised. Aminophylline and theophylline: metabolism of aminophylline and theophylline inhibited. Anti-arrhythmics: increased concentration of amiodarone, flecainide, lidocaine, procainamide and propafenone. Anticoagulants: enhanced effect of coumarins. Antiepileptics: metabolism of carbamazepine, fosphenytoin, phenytoin and valproate inhibited. Antifungals: absorption of itraconazole and ketoconazole reduced; posaconazole concentration reduced - avoid; terbinafine concentration increased. Antimalarials: avoid with artemether/lumefantrine; metabolism of chloroquine, hydroxychloroquine and quinine inhibited. Antipsychotics: possibly enhanced effect of antipsychotics, chlorpromazine and clozapine. Antivirals: concentration of atazanavir reduced; concentration of raltegravir and saquinavir possibly increased - avoid; avoid for 12 hours before and 4 hours after rilpivirine. Ciclosporin: possibly increased ciclosporin levels. Clopidogrel: possibly reduces antiplatelet effect. Cytotoxics: possibly enhances myelosuppressive effects of carmustine and lomustine; concentration of epirubicin and fluorouracil increased; avoid with dasatinib and erlotinib; possibly reduced absorption of lapatinib; possibly reduced absorption of pazopanib - give at least 2 hours before or 10 hours after cimetidine. Ergot alkaloids: increased risk of ergotism - avoid. Fampridine: avoid concomitant use. Ulipristal: contraceptive effect possibly reduced - avoid with high dose ulipristal.

Technology Process of Cimetidine

There total 65 articles about Cimetidine 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: 94.1%

(5-methyl-1H-imidazol-4-yl)methyl nitrate + 2,2'-Dithiobis(ethyl-(N-cyano-N'-methyl))guanidine → Cimetidine (51481-61-9,76181-71-0,270574-63-5,785731-92-2,752934-25-1)

Guidance literature:

(5-methyl-1H-imidazol-4-yl)methyl nitrate; With triethylamine; cobalt(II) chloride; In ethanol; for 0.166667h; Inert atmosphere;

2,2'-Dithiobis(ethyl-(N-cyano-N'-methyl))guanidine; In ethanol; at 20 ℃; for 8h; Reagent/catalyst; Solvent; Inert atmosphere;

Reference yield: 91.0%

1,3-dioxoisoindolin-2-yl 5-methyl-1H-imidazole-4-carboxylate + 2,2'-Dithiobis(ethyl-(N-cyano-N'-methyl))guanidine → Cimetidine (51481-61-9,76181-71-0,270574-63-5,785731-92-2,752934-25-1)

Guidance literature:

With tris[2-phenylpyridinato-C₂,N]iridium(III); In ethyl acetate; at 20 ℃; for 15h; Irradiation;

Reference yield: 90.0%

N-cyano-N'-methyl-N-(1-chloroethyl)guanidine + Aliquat 336 (5137-55-3,76925-99-0) + 5-methyl-4-mercaptomethylimidazole hydrochloride (70826-45-8) → cimetidine (270574-63-5,785731-92-2,752934-25-1,51481-61-9,76181-71-0)

Guidance literature:

With sodium hydroxide; In methanol; isopropyl alcohol;

upstream raw materials:

4-chloromethyl-5-methyl-imidazole hydrochloride

N-Cyano-N'-methyl-N''-(2-mercaptoethyl)guanidine

4-Bromomethyl-5-methylimidazole hydrobromide

C₁₀H₁₆N₆S

Downstream raw materials:

amoxicillin

C₈Cl₂N₂O₂*C₁₀H₁₆N₆S

N-cyano-N'-methyl-N''-<2-((5-methyl-1H-imidazol-4-yl)methylthio)ethyl>-N''-nitrosoguanidine

N-cyano-N'-methyl-N''-<2-((5-methyl-1H-imidazol-4-yl)methylthio)-ethyl>-N'-nitrosoguanidine

Refernces

• 1、 -. "Preparation method of cimetidine". Paragraph 0005; 0015; 0018; 0019; 0022; 0023; 0026; .... . Retrieved 2021/08/06.
• 2、 -. "Production method of cimetidine". Paragraph 0007; 0026; 0031-0032; 0037-0038; 0043. . Retrieved 2021/08/11.