Nizatidine

Base Information

• Chemical Name: Nizatidine
• CAS No.: 76963-41-2
• Molecular Formula: C12H21N5O2S2
• Molecular Weight: 331.463
• Hs Code.: 29349990
• European Community (EC) Number: 627-310-4
• NSC Number: 759289
• Nikkaji Number: J32.887A
• Wikipedia: Nizatidine
• NCI Thesaurus Code: C29295
• RXCUI: 42319
• Pharos Ligand ID: 4HQZJRG1FC6U
• Metabolomics Workbench ID: 42916
• ChEMBL ID: CHEMBL653
• Mol file: 76963-41-2.mol

Synonyms:Axid;LY 139037;LY-139037;LY139037;N-(2-(((2-((Dimethylamino)methyl)-4-thiazolyl)methyl)thio)ethyl)-N'-methyl-2-nitro-1,1-ethenediamine;Nizatidine

Chemical Property of Nizatidine

Chemical Property:

• Appearance/Colour: White crystalline powder
• Vapor Pressure: 2.63E-09mmHg at 25°C
• Melting Point: 130-132 °C
• Refractive Index: 1.592
• Boiling Point: 478.162 °C at 760 mmHg
• PKA: 2.1, 6.8(at 25℃)
• Flash Point: 242.984 °C
• PSA: 139.55000
• Density: 1.249 g/cm³
• LogP: 2.62750
• Storage Temp.: -20?C Freezer
• Solubility.: Sparingly soluble in water, soluble in methanol.
• Water Solubility.: 21.4g/L(temperature not stated)
• XLogP3: 1.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 9
• Exact Mass: 331.11366728
• Heavy Atom Count: 21
• Complexity: 349

Purity/Quality:

99% ^*data from raw suppliers

Nizatidine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 36

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiulcer Agents
• Canonical SMILES: CNC(=C[N+](=O)[O-])NCCSCC1=CSC(=N1)CN(C)C
• Isomeric SMILES: CN/C(=C\[N+](=O)[O-])/NCCSCC1=CSC(=N1)CN(C)C
• Recent ClinicalTrials: Phase IV Clinical Trial to Compare the Efficacy and Safety of Rebamipide/Nizatidine Combination Therapy With Nizatidine Monotherapy in Patients With Gastritis
• Uses: The value of nizatidine in the treatment of peptic ulcer disease is comparable with that of ranitidine and cimetidine. 1 or 2 times daily dosing can typically cure duodenal ulcer within 8 weeks; a single dose administration daily can prevent recurrence (Bianchi-Porro and Keohane, 1987; Stern, 1988). The efficacy of nizatidine in the treatment of stomach ulcers is similar as that of other H2-blockers but with little information available. For reflux esophagitis, Zollinger-Ellison syndrome and other kinds of peptic ulcer diseases, it is expected to generate a equal effect as ranitidine but this still needs clinical studies. It is a kind of H2 receptor antagonists. It can be used for the prevention of active duodenal ulcer, benign gastric ulcer and prevention of recurrence after the healing of the active duodenal ulcer. Histamine H2-receptor antagonist related to Ranitidine (R120000). Antiulcerative. For the treatment of acid-reflux disorders (GERD), peptic ulcer disease, active benign gastric ulcer, and active duodenal ulcer. Nizatidine is used for treating stomach and duodenum ulcers and other conditions accompanied by elevated acidity of the gastrointestinal tract.
• Drug Interactions: 1. This product can increase gastric pH, increase the midazolam absorption. Take caution when these two drugs are combined. 2. The product, when used in combination with ceftibuten, can increase the incidence of adverse reactions (such as nausea, diarrhea, headache) caused by the later one. 3. The product, if being used in combination with cefditoren, can reduce the plasma concentration of the latter one. 4. The product can increase gastric pH, resulting in decreased absorption of cefpodoxime and delavirdine. 5. This product can reduce the absorption of itraconazole, reducing its efficacy. When these two drugs are combined, the latter drug should be subject to oral administration together with cola drinks.
• Production method: Nitromethane and carbon disulfide are put into absolute ethanol; add drop wise of the ethanol solution of potassium hydroxide at 33-35 ℃, filter after the completion of the reaction; the obtained red solid was suspended in methanol, add drop wise of iodomethane at 25 ℃ and continue for the reaction. The obtained yellow crude product was recrystallized with cyclohexanone to obtain golden yellow needles of 1, 1-dimethyl-2-nitroethylene with the yield being 68%. It is then react with cysteamine hydrochloride and potassium hydroxide in a mixture solution of ethanol and water for reflux to obtain the orange 2-nitromethylene-1, 3-thiazolidine with the yield being 65%. It is then further reacted with 33% methylamine ethanol solution at room temperature to give N-(2-mercaptoethyl)-N'-methyl-2-nitro-1, l-ethylene diamine with the yield being 85%. 33% aqueous solution of dimethylamine, sodium bisulfite and 36% formaldehyde are stirred together with water. Add potassium cyanide and continue the reaction to obtain dimethylamino acetonitrile with the boiling point being 34-38 ℃/2.7kPa and the yield being 83.6%. It is further mixed with anhydrous pyridine, dry triethylamine and anhydrous methanol, put through hydrogen sulfide for being heated at 80 ℃ and then stand at room temperature to obtain dimethylamino thioacetamide with the yield being 35%. Add it to the acetone solution of 1, 3-dichloroacetone at-5 °C, making 2-dimethylaminomethyl-4-chloro-4-hydroxy-methyl-thiazoline with the yield being 72%. Dissolve it in 1, 2-dichloroethane and add drop wise of the dichloroethane solution of thionyl chloride at room temperature. After the reaction at room temperature, further have reaction at 40 ℃ to give 2-dimethylaminomethyl-4-chloromethyl-thiazole hydrochloride with the yield being 62%. Finally, it is reacted with N-(2-mercaptoethyl)-N'-methyl-2-nitro-1,1-ethylene diamine reaction in aqueous solution of sodium hydroxide to produce nizatidine and recrystallized with methanol-ethyl acetate. The finished product has a melting point being 129-132 ℃ and the yield being 52%.
• Description: Nizatidine is the fifth H2-antagonist introduced to the world market as an antiulcer agent. It is reported to be effective in the treatment of both duodenal and gastric ulcers or the prevention of their recurrences. Given once-daily, nizatidine’s bioavailability is not diminished by the concurrent administration of an antacid.
• Indications: Nizatidine is the newest H2-receptor antagonist. Similar to ranitidine, it has a relative potency twice that of cimetidine.About 90% of an oral dose is absorbed, with a peak plasma concentration occurring after 0.5 to 3 hours; inhibition of gastric secretion is present for up to 10 hours.The elimination half-life is 1 to 2 hours, and more than 90% of an oral dose is excreted in the urine.
• Clinical Use: H2 -receptor antagonist
• Drug interactions: Potentially hazardous interactions with other drugs Antifungals: absorption of itraconazole, ketoconazole and possibly posaconazole reduced, avoid with posaconazole suspension. Antivirals: concentration of atazanavir reduced; concentration of raltegravir possibly increased - avoid; avoid for 12 hours before and 4 hours after rilpivirine. Cytotoxics: avoid with dasatinib and erlotinib; possibly reduced absorption of pazopanib - give at least 2 hours before or 10 hours after nizatidine; possibly reduced absorption of lapatinib. Ulipristal: contraceptive effect possibly reduced - avoid with high dose ulipristal.

Technology Process of Nizatidine

There total 2 articles about Nizatidine 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: 81.0%

2-methylamino-2-methylthio-1-nitroethene (102721-76-6,61832-41-5) + 4-[[(2-aminoethyl)thio]-methyl]-N,N-dimethyl-2-thiazolemethanamine (78441-62-0) → nizatidine (76963-41-2)

Guidance literature:

In water; at 20 - 35 ℃; for 8h;

Reference yield:

4-Hydroxy-4-(chloromethyl)-2-<(dimethylamino)methyl>thiazoline (92759-37-0) → nizatidine (76963-41-2)

Guidance literature:

Multi-step reaction with 3 steps

1: water; potassium hydroxide / 4 h / 15 - 20 °C

2: hydrogen bromide / Reflux

3: water / 30 °C

With water; hydrogen bromide; potassium hydroxide; In water;

upstream raw materials:

2-methylamino-2-methylthio-1-nitroethene

4-[[(2-aminoethyl)thio]-methyl]-N,N-dimethyl-2-thiazolemethanamine

4-Hydroxy-4-(chloromethyl)-2-<(dimethylamino)methyl>thiazoline

Refernces

• 1、 -. "AN IMPROVED PROCESS FOR PREPARING NIZATIDINE INTERMEDIATE". Page 8,9. . Retrieved 2010/02/08.