Famotidine CAS 76824-35-6

Introduction：Basic information about Famotidine CAS 76824-35-6, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Famotidine Basic information

• Product Name: Famotidine
• Synonyms: FAMOTIDINE;[amino-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]-methyl]thio]propylidene]s;3-(((2-((aminoiminomethyl)amino)-4-thiazolyl)methyl)thio)-n-(aminosulfonyl)p;3-(((2-((diaminomethylene)amino)-4-thiazolyl)methyl)thio)-n(sup2)-sulfamoylp;Famotidine USP&BP;FAMOTIDINE, IMP. A (EP) AS HYDROCHLORIDE: 3-[[[2-[DIAMINOMETHYLENE)AMINO]THIAZOL-4-YL]METHYL]-SULPHANYL]PROPANIMIDAMIDE HYDROCHLORIDE MM(CRM STANDARD);FAMOTIDINE, IMPURITY C BP STANDARD;FAMOTIDINE, IMP. B (EP) AS DIMALONATE: 3,5-[2-[[[2-[(DIAMINOMETHYLENE)AMINO]THIAZOL-4-YL]METHYL]-SULPHANYL]ETHYL]-4H-1,2,4,6-THIATRIAZINE 1,1-DIOXIDE DIMALONATE MM(CRM STANDARD)
• CAS: 76824-35-6
• MF: C8H15N7O2S3
• MW: 337.45
• EINECS: 616-396-9
• Product Categories: Other APIs;LODINE;Amines;Heterocycles;Sulfur & Selenium Compounds;Histamine receptor;Intermediates & Fine Chemicals;Pharmaceuticals;API's;76824-35-6
• Mol File: 76824-35-6.mol

Famotidine Chemical Properties

• Melting point: 163-164°C
• Boiling point: 562.7±60.0 °C(Predicted)
• density: 1.5111 (rough estimate)
• vapor pressure: <0.0000001 kPa ( 25 °C)
• refractive index: 1.7400 (estimate)
• storage temp.: 2-8°C
• solubility: Very slightly soluble in water, freely soluble in glacial acetic acid, very slightly soluble in anhydrous ethanol, practically insoluble in ethyl acetate. It dissolves in dilute mineral acids
• pka: pKa 6.76(H2O t=23.0) (Uncertain)
• form: Solid
• color: White to Off-White
• biological source: synthetic
• Water Solubility: 1.1 mg/mL
• BCS Class: 3
• Stability: Light Sensitive
• Major Application: pharmaceutical (small molecule)
• InChI: InChI=1S/C8H15N7O2S3/c9-6(15-20(12,16)17)1-2-18-3-5-4-19-8(13-5)14-7(10)11/h4H,1-3H2,(H2,9,15)(H2,12,16,17)(H4,10,11,13,14)
• InChIKey: XUFQPHANEAPEMJ-UHFFFAOYSA-N
• SMILES: C(NS(N)(=O)=O)(=N)CCSCC1=CSC(NC(N)=N)=N1
• CAS DataBase Reference: 76824-35-6(CAS DataBase Reference)
• EPA Substance Registry System: Propanimidamide, 3-[[[2-[(aminoiminomethyl)amino]-4-thiazolyl]methyl]thio]-N-(aminosulfonyl)- (76824-35-6)

Safety Information

• Hazard Codes: T
• Risk Statements: 20/21/22-45-61
• Safety Statements: 22-24/25-53-45-36/37/39
• WGK Germany: 2
• RTECS: UA2300000
• HS Code: 29341000
• Storage Class: 11 - Combustible Solids
• Hazardous Substances Data: 76824-35-6(Hazardous Substances Data)
• Toxicity: LD50 i.v. in mice: 244.4 mg/kg (Yasufumi)

Famotidine Usage And Synthesis

Description

Famotidine (Chemical formula: C8H15N7O2S3; Brand Name: PEPCID) belongs to a histamine H2-receptor antagonist. It appears as a white to pale yellow crystalline compound. Inside the body, its primary activity is inhibiting the gastric secretion process, further reducing the acid concentration and volume of gastric secretion in the stomach. Based on this property, it is used for the treatment and prevention of ulcers occurring in the stomach and intestines. It can also treat diseases such as Zollinger-Ellison syndrome in which the stomach accumulates excess amount of acids. Moreover, it is also applied during the treatment of gastroesophageal reflux disease (GERD) and pathological hypersecretory conditions.

Reference

http://www.rxlist.com/pepcid-drug/clinical-pharmacology.htm
https://en.wikipedia.org/wiki/Famotidine

Description

Famotidine is a competitive histamine H2-receptor antagonist, and the main pharmacodynamiceffect of famotidine is to cause the inhibition of gastric secretion. Famotidine ondecomposition releases toxic products such as carbon oxides (CO, CO2), nitrogen oxides (NO, NO2), and sulphur oxides (SO2, SO3). Famotidine is a medication that is available bothin prescription and over-the-counter forms. It is used to treat conditions related to theoesophagus, stomach, and intestines. Some specific famotidine is used for the treatment ofduodenal ulcers, gastric ulcers (stomach ulcers), gastroesophageal reflux disease (GERD),and pathological hypersecretory conditions that occur when stomach acid is secreted/produced in very large quantities, an abnormal health condition called ‘Zollinger-Ellisonsyndrome’.

Chemical Properties

White Powder

Originator

Yamauouchi (Japan)

Uses

Histamine H2-receptor antagonist. Antiulcerative.

Uses

antiinflammatory

Uses

For the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD).

Uses

Use as an H2-antagonist. An anti-ulcer agent

Uses

Contact dermatitis from famotidine, a H2 -receptoragonist, was described in a nurse. In industry, threecases were reported due to intermediates of synthesis, 2-diamino-ethylene-amino-thiazolyl-methylenethiourea-dichlorideand 4-chloromethyl-2-guanidinothiazolenitrochloride.

Manufacturing Process

60.0 kg of dichloroacetone is dissolved in 550 ml of acetone. After cooling thesolution to -5°C, 55.8 kg of amidinothiourea is added to the solution undercooling portionwise at one hour intervals in a 10 kg amount ofamidinothiourea. The mixture is stirred continuously for 5 days below 0°C.The 111.6 kg resultant precipitates of N"-[4-(chloromethyl)-4,5-dihydro-4-hydroxy-2-thiazolyl]-guanidine hydrochloride are collected, and washed with50 L of acetone. In 500 ml of water are dissolved 111.6 kg of N"-[4-(chloromethyl)-4,5-dihydro-4-hydroxy-2-thiazolyl]-guanidine hydrochlorideand 32.9 kg of thiourea. The solution is stirred for one hour at 50°C. N'-[4-[[(Aminoiminomethyl)thio]methyl]-2-thiazolyl]-guanidine dihydrochloride isformed in the reaction mixture, and this reaction mixture containing thiscompound is directly used for the next process without isolation of the formedcompound.
The reaction mixture obtained is cooled below 10°C, and to the solution areadded 45.6 kg of beta-chloropropionitrile and 200 L of isopropanol. A solutionof 69.1 kg of sodium hydroxide in 280 L of water is added dropwise to thesolution under nitrogen stream followed by stirring for 2 hours at 0°C. Thecrystals precipitated are collected by filtration, and washed with cold waterand dried to provide 91.7 kg of the N"-[4-[[(2-cyanoethyl)thio]methyl]-2-thiazolyl]-guanidine, melting point 125-126.5°C.
In 60 L of anhydrous dimethylformamide is dissolved 34.3 kg of the N"-[4-[[(2-cyanoethyl)thio]methyl]-2-thiazolyl]-guanidine. After adding 60 L ofanhydrous methanol to the solution, 61.9 kg of hydrogen chloride gas ispassed through the solution below 5°C. After stirring the reaction mixture for2 days at 0°C, the reaction mixture is poured into a mixture of 350 L of water,250 kg of potassium carbonate, 30 L of ethyl acetate and ice while stirringbelow 5°C for 2 hours. The resultant precipitates are collected by filtration.After stirring a mixture of the precipitates and 400 L of water for 0.5 hour at0°, the resultant precipitates are collected by filtration, washed with 40 L ofwater and 10 L of cooled acetone respectively, and dried at reduced pressure to provide 30.6 kg of the methyl 3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propionimidate showing a melting point of 125.7°C.
In 340 L of methanol is dissolved 88.4 kg of sulfamide under heating, and thesolution is cooled to 30°C. To the solution, 114.2 kg of the methyl 3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propionimidate are addedportionwise three times while stirring at 20-30°C. (The second addition isadded 8 hours after the first addition, and the third addition is added 24 hoursafter the first addition). After stirring the reaction mixture for a further 2days, the crystals formed are collected by filtration, washed with 200 L ofcooled methanol, and air-dried at room temperature to provide 87.5 kg of the3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]-Nsulfamoylpropionamidine(generic name: famotidine) showing a melting pointof 157.6°C. Some of the obtained product is recrystallized fromdimethylformamide-water, and is dissolved in an equivalent molar amount ofaqueous acetic acid (%). To the solution is added an equivalent molar amountof a dilute sodium hydroxide solution in water to separate crystals showing amelting point of 163-164°C.

Brand name

Fluxid (Schwarz Pharma); Pepcid (Merck);Amifatidine;Famodil;Pepsidac;GASTER.

Therapeutic Function

Antiulcer

General Description

Famotidine is a histamine H2-receptor antagonist, which promotes the healing of erosive esophagitis, gastric and duodenal ulcers since it inhibits the gastric acid secretion in humans.
Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.

Biochem/physiol Actions

H2 histamine receptor antagonist; anti-ulcer agent

Contact allergens

Contact dermatitis in a nurse from famotidine, an H2-receptor agonist, was described. In industry, three cases were reported due to intermediates of the synthesis of 2-diamino-ethylene-amino-thiazolyl-methylenethio urea-dichloride, and 4-chloromethyl-2-guanidinothiaz ole-nitrochloride.

Clinical Use

Famotidine is a histamine H2-antagonist more potent than cimetidine andranitidine. Administered once or twice daily, it is useful in the treatment ofgastric, duodenal and anastomotic ulcers, upper gastrointestinal tract hemorrhage,reflux esophagitis and Zollinger-Ellison syndrome. Like ranitidine, it is lacking inantiandrogenic effects.

Synthesis

Famotidine, 3-[[[2-[(aminomethyl)amino]-4-thiazolyl] methyl]thio]-N-(aminosulfonyl)propanimidamide (16.2.13), is synthesized from S-(2-aminothiazol-4-ylmethyl)isothiourea (16.2.9), which is synthesized by reacting 1,3-dichloroacetone with twomolecules of thiourea, during which a thiazol ring is formed and the chlorine atom is substituted,giving an intermediate 2-amino-5-chlormethylthiazol. Reacting this with 2-chlorpropionitrilegives S-(2-aminothiazol-4-yl-methyl)-2-cyanoethane (16.2.10), which in turn isreacted with benzoylizthiocyanate. The resulting benzoylthiourea derivative (16.2.11) firstundergoes S-methylation by methyliodide and further cleaved by ammonia into 3-[[[2-(aminomethyl)amino]-4-thiazolyl]-methyl]thio]ethylcyanide (16.2.12). Successivemethanolysis of the nitrile group and subsequent reaction of the resulting iminoether withsulfonamide gives famotidine (16.2.13).

Veterinary Drugs and Treatments

In veterinary medicine, famotidine may be useful for the treatmentand/or prophylaxisof gastric, abomasal and duodenal ulcers,uremic gastritis, stress-related or drug-induced erosive gastritis,esophagitis, duodenal gastric reflux, and esophageal reflux.
Famotidine has fewer drug interactions and activity may persistlonger than cimetidine.

Drug interactions

Potentially hazardous interactions with other drugs
Antifungals: absorption of itraconazole and ketoconazole reduced; concentration of posaconazole possibly reduced - avoid with suspension.
Antivirals: concentration of atazanavir reduced - adjust doses of both drugs; concentration of raltegravir possibly increased - avoid; avoid for 12 hours before and 4 hours after rilpivirine.
Ciclosporin: possibly increased ciclosporin levels.
Cytotoxics: possibly reduced dasatinib concentration - avoid if possible; avoid with erlotinib; possibly reduced absorption of pazopanib - give at least 2 hours before or 10 hours after famotidine; possibly reduced absorption of lapatinib
. Ulipristal: contraceptive effect possibly reduced - avoid with high dose ulipristal.

Metabolism

Metabolism of famotidine occurs in the liver, with formation of an inactive metabolite, the sulfoxide.
Following oral administration, the mean urinary excretion of famotidine is 65-70% of the absorbed dose, 25-30% as unchanged compound. Renal clearance is 250-450 mL/min, indicating some tubular excretion. A small amount may be excreted as the sulfoxide.

storage

Store at -20°C

Famotidine Preparation Products And Raw materials

• Raw materials: 1,3-Dichloroacetone-->Amidinothiourea-->Sulfamide-->4-(CHLOROMETHYL)THIAZOLE HYDROCHLORIDE-->Sodium hydroxide-->Hydrochloric acid-->3-Chloropropiononitrile
• Preparation Products: FaMotidine AMide IMpurity