103577-45-3 Usage
Uses
1. Used as a gastric proton pump inhibitor and an antiulcerative.
2. Used in the treatment of acid-reflux disorders (GERD), peptic ulcer disease, H. pylori eradication, and prevention of gastrointestinal bleeds with NSAID use.
3. Used in the treatment of gastroesophageal reflux disease (GERD), erosive esophagitis, duodenal ulcers, Helicobacter pylori (H. pylori) infections, stomach ulcers, and prevention of stomach ulcers in those people taking non-steroidal anti-inflammatory drugs (NSAIDs).
4. Used as an H+,K+-ATPase inhibitor that displays antisecretory activity.
Application Industries:
1. Pharmaceutical Industry: Lansoprazole is used for the treatment of various gastrointestinal disorders, such as GERD, erosive esophagitis, stomach ulcers, duodenal ulcers, H. pylori infections, and Zollinger-Ellison syndrome.
2. Medical Industry: Lansoprazole is used to prevent gastrointestinal bleeds in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) and to treat acid-reflux disorders.
Brief Introduction
Lansoprazole is in a class of drugs called proton pump inhibitors (PPI) which prevent the stomach from producing gastric acid.The other drugs in PPI family include:
rabeprazole (Aciphex),
omeprazole (Prilosec),
pantoprazole (Protonix),
esomeprazole (Nexium).
Proton pump inhibitors are used for the treatment of conditions such as ulcers, gastroesophageal reflux disease (GERD) and Zollinger-Ellison syndrome that are caused by stomach acid. Lansoprazole, like other proton-pump inhibitors, blocks the enzyme in the
wall of the stomach that produces acid. By blocking the enzyme, the production of acid is decreased, and this allows the stomach and esophagus to heal.
Gastric acid secretion inhibitor
R-(+)-Lansoprazole is the dextroisomer of lansoprazole and a kind of anti-ulcer drug. It is the substitution product of benzimidazole derivative byimporting the fluorine element in the molecular structure and the is the second proton pump inhibitor after omeprazole.? R-(+)-Lansoprazole has a better inhibitory effect for gastric acid secretion than that of other drugs (omeprazole, pantoprazole, rabeprazole) and it can significantly inhibit ulcer. It has a better Curative effect for ethanol-induced gastric mucosa lesion and acid hypersecretion induced duodenal ulcer than that of famotidine and omeprazole. In addition, This product also has an anti-Helicobacter pylori effect similar to that of Bismuth preparations and can be used to treat reflux esophagitis and Zollinger-Ellison syndrome.
pharmacodynamics???
R-(+)-Lansoprazole can transform into active sulfonamide derivatives. In the tubule acidic environment of parietal cells, which are connected to the sulfydryl of H+-K+-(ATP)adenosine triphosphatase(the last step of the enzyme catalyzed gastric acid secretion process),passivat H+-K+-ATP enzyme and Inhibit the gastric acid secretion regulated by central and peripheral nervous systems. The inhibition effect of gastric acid secretion of this product is at least as strong as omeprazole. In vivo studies of animal model have demonstrated that the inhibition effect for gastric acid secretion of R-(+)-Lansoprazole is inferior to H2 receptor antagonist ranitidine and famotidine, but just as effective as omeprazole. Unlike the H2 receptor antagonist, whether taken in the morning or evening, this product can inhibit gastric acid secretion during the day and night. It can also reduce the gastric acid secretion, inhibit the secretion of pepsin and its activity and clear pyloric campylobacter on gastric mucosa (A bacterium of causing recurrence. of peptic ulcer).
It can also be used to treat Helicobacter pylori infection, alongside antibiotics as adjunctive treatment, to kill H. pylori causing ulcers or other problems involves using two other drugs known as "triple therapy", and involves taking twice daily for 10 or 14 days lansoprazole, amoxicillin, and clarithromycin.
Pharmacokinetics
When this product transform into active AG-1812 and AG-2000, R-(+)-Lansoprazole in serum is metabolized quickly and completely into two main faeces: Lansoprazole sulfone and hydroxy orchid sola. About 14%~23% of doses are excreted in the urine as conjugated and non-conjugated hydroxylation metabolites and no prototype of this product is found. The half-life of this product is 1.3~1.7 h, about 2 h for elderly people and as long as 7 h for patients with severe liver failure. The Peak blood concentration can reach 1038μg/L within 2 h after taking 30 mg enteric capsules of this product.
Marketing internationally
The lansoprazole molecule is off-patent and so generic drugs are available under many brand names in many countries;there are patents covering some formulations in effect as of 2015.
Since 2009, lansoprazole has been sold over the counter (OTC) in the U.S. in a marketed by Novartis as Prevacid 24HR. In Australia, it is being marketed by Pfizer as Zoton.
Clinical application
Applied to reflux esophagitis, gastric ulcer, duodenal ulcer. Patients with duodenal ulcer take this product 30 mg a day for a period of 2～4 weeks. An cure efficiency rate of 75%～100% can be achieved.It cures faster than famotidine and omeprazole and reduces ulcers-induced pain faster thanranitidine. Taking this product 30 mg a day can effectively treat reflux esophagitis and the cure rates after 4 weeks and 8 weeks can reach? 63%～84% and 85%～92% respectively. The cure effect for reflux esophagitis of this product is better than ranitidine and comparative to omeprazole. After 4 weeks treatment, the alleviation effect for heartburn symptoms of this product is much better than that of ranitidine and omeprazole. R-(+)-Lansoprazole can effectively treat patients with Peptic ulcer and reflux esophagitis whom cannot be cured by H2 receptor antagonist. A cure rate of 69%～100% can be achieved by taking this product 30 mg a day for a period of 8 weeks. A higher cure rate can be achieved if the dosage is increased to 30mg a day.
Drug interactions
1. Take R-(+)-Lansoprazole in conjunction with acetaminophen can increase the Peak blood concentration and shorten the time to peak.
2. Take R-(+)-Lansoprazole in conjunction with Roxithromycin can increase the local concentration of the latter and has a synergistic effect when treating Hp infection.
3. Take R-(+)-Lansoprazole in conjunction with antacids can reduce the bioavailability of this product. If necessary, this product should be taken after 1 hour use of antacids.
4. Take R-(+)-Lansoprazole in conjunction with theophylline can slightly reduce the? blood concentrations of theophylline.
5. R-(+)-Lansoprazole can inhibit gastric acid secretion significantly and persistently, thereby reduce the absorption of itraconazole and ketoconazole. So they should not be used at the same time.
6. Sucralfate may interfere the absorption of this product and reduce its bioavailability. So this product should be taken at least 30 minutes before taking sucralfate.
7. Take R-(+)-Lansoprazole in conjunction with clarithromycin may cause? Glossitis, stomatitis and black tongue. Patients should pay attention to the change of oral mucosa , stop using clarithromycin and reduce the dose of this product if necessary.
Adverse reactions
This product can cause constipation, diarrhea, dry mouth, abdominal distention, anemia, increased white blood cells and eosinophils, thrombocytopenia, elevated liver enzymes, headache, drowsiness, insomnia, skin rashes, itching, etc., and occasionally cause fever, increased total cholesterol and uric acid value, etc.
Cautions
1.This drug is forbidden for those who are allergic to this product, pregnant and lactant women. Patients with a history of drug allergy
and hepatic insufficiency should use this product with caution.
2.Elderly patients with medication must be closely observed
3.This product may mask the stomach cancer symptoms. Therefore, this product should be taken before excluding stomach cancer.
Originator
Takeda (Japan)
Manufacturing Process
Preparation of 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methylthio-1Hbenzimidazole:A mixture of 6.63 g of 2-hydroxymethyl-3-methyl-4-(2,2,2-trifluoroethoxy)
pyridine (30 mmol), 4.5 g of 2-mercaptobenzimidazol (30 mmol) and 8.67 g
of triphenylphosphine (33 mmol) was dissolved in 100 ml of tetrahydrofuran,
5.75 g of diethyl azodicarboxylate (33 mmol) dissolved in 30 ml of
tetrahydrofuran was added dropwise thereto at room temperature, and stirred
for 1 hour. The reaction mixture was concentrated under a reduced pressure,
the resulting residue was combined with 100 ml of ethylacetate, and extracted
twice with 50 ml portions of 1 N HCl. The aqueous layer was then washed
with 50 ml of diethylether; neutralized with 1 N NaOH to adjust the pH to 7.
The resulting precipitates were filtrated, washed with water, and dried, to
obtain 10.06 g of 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methylthio-
1H-benzimidazole as a white solid (yield: 95%), m.p.142-144°C.4.46 g of 2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methylthio-1Hbenzimidazole (12 mmol) and 18.74 mg of tetramethyl-1-piperidinyloxy free
radical (1 mol %, used as a catalyst) were dissolved in 40 ml of
tetrahydrofuran, and combined with 166.76 mg of tetrabutylammonium
chloride (5 mol %) dissolved in 20 ml of distilled water. The resulting mixture
was cooled to 0°C and 13.6 ml of NaOCl (12%, 2.2 equivalent) dissolved in 20
ml of distilled water was added thereto over 2 hours at 0°C, stirred for 10
min, and then for additional 10 min at 20°C. Then, the reaction mixture was
extracted with 40 ml of ethylacetate and the organic layer was washed with
sat. NaHCO3 (30 ml) and then with sat. brine (30 ml), dried over anhydrous
MgSO4, and the solvent was removed therefrom. The resulting crude product
as recrystallized from acetone/hexane, to obtain 3.99 g of 2-[3-methyl-4-
(2,2,2-trifluoroethoxy)-2-pyridyl]methylsulphinyl-1H-benzimidazol
(lansoprazole) as a white-light brown solid (yield: 90%), melting point 164-
165°C (decomposition).
Therapeutic Function
Antiulcer
Biological Activity
H + ,K + -ATPase inhibitor (IC 50 = 6.3 μ M) that displays antisecretory and antiulcer activity. Inhibits gastric acid secretion (IC 50 = 0.09 μ M for histamine-induced acid formation) and reduces gastric lesion formation induced by a variety of ulcerative stimuli. Antibacterial against Helicobacter pylori in vitro . Also blocks swelling-dependent chloride channel (ICIswell) in NIH3T3 fibroblasts. More potent than omeprazole (5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole ).
Biochem/physiol Actions
Gastric proton pump inhibitor.
Check Digit Verification of cas no
The CAS Registry Mumber 103577-45-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,0,3,5,7 and 7 respectively; the second part has 2 digits, 4 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 103577-45:
(8*1)+(7*0)+(6*3)+(5*5)+(4*7)+(3*7)+(2*4)+(1*5)=113
113 % 10 = 3
So 103577-45-3 is a valid CAS Registry Number.
InChI:InChI=1/C17H14F3N3O2/c1-10-13(21-7-6-15(10)25-9-17(18,19)20)8-14(24)16-22-11-4-2-3-5-12(11)23-16/h2-7H,8-9H2,1H3,(H,22,23)
103577-45-3Relevant articles and documents
Synthesis method of lansoprazole
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Paragraph 0047-0075, (2021/04/28)
The invention discloses a synthesis method of lansoprazole, which comprises the following steps: condensing 2-mercaptobenzimidazole and 2-chloromethyl-3-methyl-4-(2, 2, 2-trifluoroethoxy) pyridine hydrochloride under alkaline conditions, oxidizing by a one-pot method to obtain a lansoprazole crude product, and finally refining to obtain the lansoprazole refined product. The method solves the problems that many three wastes are generated in lansoprazole production, a plurality of refining is needed, and drying deterioration is easily caused; the method is mild in reaction conditions, the total molar yield is 92% or above, the HPLC is 99.9% or above, and the method is suitable for industrial large-scale production.
Enhanced Antigiardial Effect of Omeprazole Analog Benzimidazole Compounds
Arreguin-Espinosa, Roberto,Calderón-Jaimes, Ernesto,Cuevas-Cruz, Miguel,Gómez-Manzo, Saúl,Hernández-Ochoa, Beatriz,Méndez-Tenorio, Alfonso,Marcial-Quino, Jaime,Ramírez-Nava, Edson Jiovany,Rocha-Ramírez, Luz María,Sánchez-Carrillo, Adrián,Santos-Segura, Araceli
, (2020/09/18)
Giardiasis is a diarrheal disease that is highly prevalent in developing countries. Several drugs are available for the treatment of this parasitosis; however, failures in drug therapy are common, and have adverse effects and increased resistance of the parasite to the drug, generating the need to find new alternative treatments. In this study, we synthesized a series of 2-mercaptobenzimidazoles that are derivatives of omeprazole, and the chemical structures were confirmed through mass, 1H NMR, and 13C NMR techniques. The in vitro efficacy compounds against Giardia, as well as its effect on the inhibition of triosephosphate isomerase (TPI) recombinant, were investigated, the inactivation assays were performed with 0.2 mg/mL of the enzyme incubating for 2 h at 37 ?C in TE buffer, pH 7.4 with increasing concentrations of the compounds. Among the target compounds, H-BZM2, O2N-BZM7, and O2N-BZM9 had greater antigiardial activity (IC50: 36, 14, and 17 μM on trophozoites), and inhibited the TPI enzyme (K2: 2.3, 3.2, and 2.8 M?1 s?1) respectively, loading alterations on the secondary structure, global stability, and tertiary structure of the TPI protein. Finally, we demonstrated that it had low toxicity on Caco-2 and HT29 cells. This finding makes it an attractive potential starting point for new antigiardial drugs.
Stable high-purity (R)-Lansoprazole, and preparation method thereof
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Paragraph 0056-0058, (2019/09/14)
The invention provides (R)-Lansoprazole with a purity of 99.5% or higher. The preparation method comprises following steps: a (R)-Lansoprazole crude product is dissolved in a refined solvent system, dissolving and condensation are carried out, and then crystallization, filtering, and impurity removing are carried out to obtain refined (R)-Lansoprazole, wherein in the dissolving preparation process, an alkaline stabilizing agent 1 is added, and in the condensation process, an alkaline stabilizing agent 2 is added, so that the impurity I content of the obtained (R)-Lansoprazole refined product is lower than 0.1%, degradation impurity introduction is controlled preferably, in long term storage process, the obtained product is capable of satisfying medicine purity requirements, the controllability is high, and a quality control problem of (R)-Lansoprazole in industrialized production is solved.
Preparation method of dexlansoprazole
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Paragraph 0038; 0039; 0040; 0044; 0048; 0052, (2018/08/04)
The invention relates to a preparation method of dexlansoprazole. The method includes: preparation of the formula (I) compound into dexlansoprazole by substitution in the presence of a trifluoroethanol metal salt. The method has a simple process, and can acquire high yield and high purity dexlansoprazole without column chromatography, and is very suitable for industrial mass production.
Method for preparing lansoprazole
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Page/Page column 7-16, (2019/01/08)
The invention belongs to the field of medicinal chemistry and in particular relates to a method for preparing lansoprazole. The method disclosed by the invention comprises the following reaction steps: carrying out an addition reaction on acraldehyde and trifluoroethanol to produce a compound IV, chlorinating 2-mercapto benzimidazole to condense with 3-hydroxy-2-butanone, performing rearrangementto produce a compound VI, performing condensation on the compounds IV and VI and ammonia to produce a compound VII, and further oxidizing the compound VII, thereby obtaining the lansoprazole I. The method disclosed by the invention has the advantages that the reaction does not involve strong acids such as sulfuric acid and nitric acid, and emission of three wastes is reduced while convenience is brought to after-treatment; and the reaction step is short, and the total yield is high and can reach 41-62%. The cost per kilogram is one half that of the conventional process, and cheap and high-quality bulk drugs are provided for the preparation.
Method for preparing benzimidazole proton pump inhibitor
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Paragraph 0049; 0050; 0051; 0053; 0054; 0055; 0056-0058, (2018/09/08)
The invention provides a novel method for preparing a benzimidazole proton pump inhibitor, and belongs to the field of medicine synthesis. According to the method provided by the invention, a complexformed by using graphene oxide and a transition metal salt is used as a catalyst, and the corresponding benzimidazole proton pump inhibitor is obtained through oxidizing a thioether by an oxidizing agent under an alkaline condition in an organic solvent. The method has the advantages of mild reaction condition, high yield, environmental friendliness, and less impurity, the catalyst can be recycled, and the method is suitable for industrial production.
Method for preparing high-purity razole intermediate and medicine by using green technology instead of phosgene, thionyl chloride and other toxic and harmful substances
-
, (2017/09/01)
The invention discloses a method for preparing a high-purity razole intermediate and a medicine by using a green technology instead of phosgene, thionyl chloride and other toxic and harmful substances. The preparation method comprises the following steps: dissolving Ph3PO in an organic solvent, placing the obtained solution in a reaction bottle, dropwise adding BTC to form a high-efficiency chloration reagent, carrying out a heat insulation reaction for a period of time after the dropwise addition is finished, dissolving a razole hydroxide in the organic solvent, dropwise adding the obtained solution to the above system, carrying out a heat insulation reaction for a period of time, carrying out suction filtration, and drying the obtained dried reaction product to obtain razole chloride. In the process, the Ph3PO is equivalently regenerated, a mother liquor part is concentrated to precipitate the Ph3PO at a low temperature, and the Ph3PO can be repeatedly used after being washed with a solvent with small polarity. The method has the advantages of few side reactions, high product quality, few "three wastes" pollutions, high atomic economy, and good promotion and application prospect. The invention also provides a relevant razole medicine prepared from the razole chloride obtained through the green technology. The medicine has obviously higher purity than medicines obtained through traditional methods.
Preparation technology of lansoprazole
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Paragraph 0042, (2017/08/30)
The invention provides a preparation technology of lansoprazole. The preparation technology comprises the following steps that 1, a raw material A 2-mercapto benzimidazole is dissolved into methanol in the presence of alkali, a raw material B 2-chloromethyl-3-methyl-4-(2,2,2,-trifluoroethoxyl)pyridine hydrochloride is added for a reaction, filtering is conducted by adding water, obtained precipitates are washed and dried, and then an intermediate C [[[3-methyl-4-(2,2,2,-trifluoroethoxyl)-2-pyridyl]methyl]sulfydryl]-H-benzimidazole is obtained; the intermediate C is dissolved into ethanol, a mixed solution of hydrogen peroxide, a catalyst and ethanol is added for a reaction, filtering is conducted by adding water, obtained precipitates are washed, and then the lansoprazole is obtained. According to the preparation technology, the yield is increased, the cost is reduced, the production cycle is shortened, and the preparation technology is more suitable for industrialized production.
Refining method for lansoprazole crude product
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Paragraph 0032; 0034, (2017/09/02)
The invention discloses a refining method for a lansoprazole crude product. The method includes: firstly dissolving the crude product, performing decoloration, then conducting cooling and filtration to obtain a solid, and subjecting the obtained solid to refrigeration crystallization treatment in a mixed solvent of propylene oxide/tetrahydrocarbon furan/dichloromethane, and carrying out filtering, washing and drying on the obtained crystal so as to obtain a refined lansoprazole product. According to the method, a refined lansoprazole product with extremely high yield and low impurities can be obtained by one treatment, and the prepared refined lansoprazole product does not contain water or solvate of ethanol, has yield up to 83%-88%, purity of not less than 99.76%, and the content of impurities sulfide and sulfone respectively lower than 0.07% and 0.14%.
Preparation method of (R)-lansoprazole
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Paragraph 0018; 0019; 0020; 0024; 0028; 0029, (2017/10/27)
The invention provides a preparation method of (R)-lansoprazole. Through a condensation reaction and an asymmetric oxidation reaction of thioether, the (R)-lansoprazole is prepared. The preparation method comprises refining a (R)-lansoprazole finished product. In the first reaction step, cheap sodium hydroxide replaces sodium methylate, a reaction temperature is reduced to the room temperature from a return temperature, ethanol is used as a solvent and a high yield of 99.5% is realized. In the second asymmetric oxidation step, a yield is 80% or more. The preparation method has simple processes, is free of multiple complex extraction and separation processes and is suitable for industrial production. In the third step, through reaction condition optimization, a reaction conversion rate is greater than 85% and enantioselectivity is greater than 97%. Through purification, the product quality satisfies the FDA same-type product standards, optical purity and chemical purity are greater than 99.5%, the content of thioether is less than 0.1% and sulphone content is less than 0.1%. The preparation method has stable processes and an industrialization prospect.
