Famotidine Chemical Properties

Melting point:

163-164°C

Boiling point:

562.7±60.0 °C(Predicted)

Density 

1.5111 (rough estimate)

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

Water Solubility 

1.1 mg/mL

BCS Class

3

Stability:

Light Sensitive

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

Hazardous Substances Data

76824-35-6(Hazardous Substances Data)

Toxicity

LD50 i.v. in mice: 244.4 mg/kg (Yasufumi)

MSDS

• Language:English Provider:Famotidine
• Language:English Provider:SigmaAldrich

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 pharmacodynamic effect of famotidine is to cause the inhibition of gastric secretion. Famotidine on decomposition 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 both in prescription and over-the-counter forms. It is used to treat conditions related to the oesophagus, stomach, and intestines. Some specific famotidine is used for the treatment of duodenal 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-Ellison syndrome’.

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 -receptor agonist, was described in a nurse. In industry, three cases were reported due to intermediates of synthesis, 2- diamino-ethylene-amino-thiazolyl-methylenethiourea-dichloride and 4-chloromethyl-2-guanidinothiazolenitrochloride.

Manufacturing Process

60.0 kg of dichloroacetone is dissolved in 550 ml of acetone. After cooling the solution to -5°C, 55.8 kg of amidinothiourea is added to the solution under cooling portionwise at one hour intervals in a 10 kg amount of amidinothiourea. 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 with 50 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 hydrochloride and 32.9 kg of thiourea. The solution is stirred for one hour at 50°C. N'-[4- [[(Aminoiminomethyl)thio]methyl]-2-thiazolyl]-guanidine dihydrochloride is formed in the reaction mixture, and this reaction mixture containing this compound is directly used for the next process without isolation of the formed compound.
The reaction mixture obtained is cooled below 10°C, and to the solution are added 45.6 kg of beta-chloropropionitrile and 200 L of isopropanol. A solution of 69.1 kg of sodium hydroxide in 280 L of water is added dropwise to the solution under nitrogen stream followed by stirring for 2 hours at 0°C. The crystals precipitated are collected by filtration, and washed with cold water and 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 of anhydrous methanol to the solution, 61.9 kg of hydrogen chloride gas is passed through the solution below 5°C. After stirring the reaction mixture for 2 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 stirring below 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 at 0°, the resultant precipitates are collected by filtration, washed with 40 L of water 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 the solution is cooled to 30°C. To the solution, 114.2 kg of the methyl 3-[[[2- [(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propionimidate are added portionwise three times while stirring at 20-30°C. (The second addition is added 8 hours after the first addition, and the third addition is added 24 hours after the first addition). After stirring the reaction mixture for a further 2 days, the crystals formed are collected by filtration, washed with 200 L of cooled methanol, and air-dried at room temperature to provide 87.5 kg of the 3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]-Nsulfamoylpropionamidine (generic name: famotidine) showing a melting point of 157.6°C. Some of the obtained product is recrystallized from dimethylformamide-water, and is dissolved in an equivalent molar amount of aqueous acetic acid (%). To the solution is added an equivalent molar amount of a dilute sodium hydroxide solution in water to separate crystals showing a melting 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 and ranitidine. Administered once or twice daily, it is useful in the treatment of gastric, duodenal and anastomotic ulcers, upper gastrointestinal tract hemorrhage, reflux esophagitis and Zollinger-Ellison syndrome. Like ranitidine, it is lacking in antiandrogenic 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 two molecules 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-chlorpropionitrile gives S-(2-aminothiazol-4-yl-methyl)-2-cyanoethane (16.2.10), which in turn is reacted with benzoylizthiocyanate. The resulting benzoylthiourea derivative (16.2.11) first undergoes S-methylation by methyliodide and further cleaved by ammonia into 3-[[[2- (aminomethyl)amino]-4-thiazolyl]-methyl]thio]ethylcyanide (16.2.12). Successive methanolysis of the nitrile group and subsequent reaction of the resulting iminoether with sulfonamide gives famotidine (16.2.13).

Veterinary Drugs and Treatments

In veterinary medicine, famotidine may be useful for the treatment and/or prophylaxis of 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 persist longer 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(76824-35-6)Related Product Information

• Methylchloroisothiazolinone/methylisothiazolinone mixture (MCIT/MIT)
• Basic Violet 1
• Methyl salicylate
• METSULFURON METHYL
• N-Aminothiourea
• Sodium thiosulfate
• Sulfamide
• Thioacetamide
• Tribenuron methyl
• Sulfanilamide
• Kresoxim-methyl
• Methyl acrylate
• N-Acetylsulfanilyl chloride
• Methanol
• Benzothiazole
• Methylparaben
• Methyl
• [3-[[[2-(DiaMinoMethyleneaMino)-4-thiazolyl]Methyl]thio]propionyl]sulfaMide Hydrochloride (FaMotidine IMpurity)