73590-58-6 Usage
Description
Omeprazole is a potent gastric antisecretory agent with selective inhibitory effect on the
H+,K+-ATPase proton pump. It is highly effective in the treatment of duodenal ulcer and
Zollinger-Ellison syndrome, and is reportedly superior to ranitidine in the management of
reflux esophagitis.
Chemical Properties
White Crystalline Solid
Originator
Astra (Sweden)
Uses
Omeprazole is a proton pump inhibitor used to treat diseases like gastroesophageal reflux disease (GERD), used for gastric and duodenal ulcers, reflux or erosive esophagitis, and Zollinger-Ellison syndrome. It is also effective for gastric and duodenal ulcers that are ineffective with H2 receptor antagonists. Injections of Omeprazole can also be used for: 1 gastrointestinal bleeding, such as peptic and anastomic ulcer bleeding, and the prevention of severe diseases (such as cerebral hemorrhage, severe trauma, etc.) and gastric surgery caused by upper intestinal bleeding; 2 acute gastric mucosal damage complicated by stress or nonsteroidal anti-inflammatory drugs; 3 general anesthesia, post-surgery, or coma patients, to prevent acid reflux and aspiration pneumonia; 4 Combined with amoxicillin and clarithromycin, or with metronidazole and clarithromycin, it can effectively kill Helicobacter pylori (Hp).
Preparation
The antiulcer agent omeprazole is produced from 2,3,5-trimethylpyridine N-oxide.Synthesis and Structure of OmeprazoleSteps: 2-(Lithium methyl sulphinyl)-5-methoxy-1H benzimidazole 20g was reacted with 2-chloro-3,5-dimethyl-4-methoxy pyridine 21 g to form sulphide intermediate and then converted to Omeprazole when treated with m-CPBA which used as anoxidizingagents. The acetamide-sulfide compounds modification are oxidised to form the amide sulfinyl compound and gives the sulfinyl carboxylate or salts upon alkaline hydrolysis.On further decarboxylation leads to the target molecules. The residual, unreacted salt, inorganic by-products and other minor by-products can be easily purified by a simple washing from omeprazole or lansoprazole. The amide compounds containing crystalline solids as opposed to the sulphide and sulfoxides of the reported procedures.DOI: http://dx.doi.org/10.20902/IJPTR.2019.120307
Application
Omeprazole is a benzimidazole with selective and irreversible proton pump inhibition activity. Omeprazole forms a stable disulfide bond with the sulfhydryl group of the hydrogen-potassium (H+ - K+) ATPase found on the secretory surface of parietal cells, thereby inhibiting the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen and suppressing gastric acid secretion. This agent exhibits no anticholinergic activities and does not antagonize histamine H2 receptors. Omeprazole Pellets are used in the treatment of Gastroesophageal reflux disease (GERD): A condition in which backward flow of acid from the stomach causes heartburn and injury of the food pipe (esophagus).
Definition
ChEBI: Omeprazole is a member of the class of benzimidazoles that is 1H-benzimidazole which is substituted by a [4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl group at position 2 and a methoxy group at position 5.
Brand name
Prilosec (Astra Zeneca).
Therapeutic Function
Antiulcer
World Health Organization (WHO)
Omeprazole was introduced in the 1980s. It belongs to a group of
agents that have an inhibitory effect on the secretion of hydrochloric acid in the
stomach (gastric acid proton pump inhibitors) and is used in the treatment of
upper gastrointestinal tract disorders. The Committee for Proprietary Medicinal
Products of the European Commission has concluded that a causal association
between the reactions reported in Germany and the use of omeprazole had not
been established. Nevertheless oral administration should be preferred.
(Reference: (CPMPPO) Pharmacovigilance Opinion, No.16 , , 25 July 1994)
General Description
Omeprazole, 5-methoxy-2-(((4-methoxy-3, 5-dimethyl-2-pyridinyl)methyl) sulfinyl)-1Hbenzimidazole(Losec), is a white to off-white crystallinepowder with very slight solubility in water. Omeprazole isan amphoteric compound (pyridine N, pKa 4.06; benzimidazoleN-H, pKa 0.79), and consistent with the proposedmechanism of action of the substituted benzimidazoles, isacid labile. Hence, the omeprazole product is formulatedas delayed-release capsules containing enteric-coatedgranules.The absolute bioavailability of orally administeredorneprazole is 30% to 40% related to substantial first-passbiotransformation. The drug has a plasmahalf-life of about 1 hour. Most (77%) of an oral dose ofomeprazole is excreted in the urine as metabolites with insignificantantisecretory activity. The primary metabolitesof omeprazole are 5-hydroxyomeprazole (CYP2C19) andomeprazole sulfone (CYP3A4). The antisecretory actions ofomeprazole persist for 24 to 72 hours, long after the drughas disappeared from plasma, which is consistent with itssuggested mechanism of action involving irreversible inhibitionof the proton pump.Omeprazole is approved for the treatment of heartburn,GERD, duodenal ulcer, erosive esophagitis, gastric ulcer,and pathological hypersecretory conditions.
Biological Activity
H + ,K + -ATPase inhibitor (IC 50 = 5.8 μ M) that displays antisecretory and antiulcer activity. Inhibits gastric acid secretion (IC 50 = 0.16 μ M for histamine-induced acid formation) and reduces gastric lesion formation induced by a variety of ulcerative stimuli. Antibacteral against Helicobacter pylori in vitro . Also inhibits CYP2C19, CYP2C9 and CYP3A (K i values are 3.1, 40.1 and 84.4 μ M respectively) and blocks swelling-dependent chloride channels (ICIswell).
Biochem/physiol Actions
Omeprazole binds covalently to proton pump (H+, K+-ATPase) and inhibits gastric secretion. It is useful in ameliorating the effects of peptic oesophagitis, duodenal and gastric ulcer. Omeprazole is preferred over antagonists of histamine H2-receptor and ranitidine for its higher efficiency. It is also useful in treating Zollinger-Ellison syndrome.
Clinical Use
Omeprazole is a proton-pump inhibitor used in the management and treatment of several conditions, including uncomplicated heartburn, peptic ulcer disease, gastrointestinal reflux disease, Zollinger-Ellison syndrome, multiple endocrine adenomas, systemic mastocytosis, erosive esophagitis, gastric ulcers, and helicobacter pylori infection.
Veterinary Drugs and Treatments
Omeprazole is potentially useful in treating both gastroduodenal
ulcer disease and to prevent or treat gastric erosions caused by
ulcerogenic drugs (e.g., aspirin). An oral paste product is labeled
for the treatment and prevention of recurrence of gastric ulcers in
horses.
Drug interactions
Potentially hazardous interactions with other drugs
Anticoagulants: effect of coumarins possibly
enhanced. Antiepileptics: effects of phenytoin possibly
enhanced.
Antifungals: absorption of itraconazole and
ketoconazole reduced; avoid with posaconazole;
concentration increased by voriconazole.
Antivirals: reduced atazanavir concentration
- avoid; AUC of saquinavir increased by 82%
(increased risk of toxicity) - avoid; concentration of
raltegravir possibly increased - avoid; concentration
of rilpivirine reduced - avoid; concentration of
omeprazole reduced by tipranavir.
Ciclosporin: variable response; mostly increase in
ciclosporin level.
Cilostazol: increased cilostazol concentration -
reduce cilostazol dose.
Clopidogrel: avoid due to reduced efficacy of
clopidogrel.
Cytotoxics: possibly reduced excretion of
methotrexate; avoid with erlotinib and vandetanib;
possibly reduced dasatinib and lapatinib absorption
- avoid with dasatinib; possibly reduced absorption
of pazopanib.
Tacrolimus: may increase tacrolimus concentration.
Ulipristal: reduced contraceptive effect, avoid with
high dose ulipristal.
Metabolic pathway
When male humans are given 14C-omeprazole orally,
an average of 79% of the dose is recovered in the
urine in 96 h. Omeprazole is completely metabolized
and at least six metabolites are identified. Two major
metabolites are hydroxyomeprazole and omeprazole
acid.
Metabolism
Omeprazole is completely metabolised in the liver by the
cytochrome P450 system to form inactive metabolites
which are excreted mostly in the urine and to a lesser
extent in bile. CYP2C19 produces hydroxyomeprazole,
the major metabolite, CYP3A4 produces omeprazole
sulphone.
Mode of action
Omeprazole is a proton pump inhibitor which can specifically act on gastric parietal cell proton pump sites and transform into the active form of sulfonamide, then irreversibly binds to the proton pumps through disulfide bonds, generating a sulfonamide and proton pump compound (H + -K + -ATP), thereby inhibiting the enzymatic activity, preventing the H+ in parietal cells from being transported to the stomach cavity. It has a strong and persistent inhibitory role on gastric acid secretion caused by basal gastric acid and pentapeptide gastric acid secretions, greatly reducing gastric acid within the gastric juice. Rapid, reversible, and no H2 antagonist-induced psychiatric side effects.
References
1) Satoh?et al.?(1989),?Antisecretory and antiulcer activities of a novel proton pump inhibitor AG-1749 in dogs and rats; J. Pharmacol. Exp. Ther.,?248?8062) Kuzin?et al.?(2018),?Effects of the Proton Pump Inhibitors Omeprazole and Pantoprazole on the Cytochrome P450-Mediated Metabolism of Venlafaxine; Clin. Pharmacokinet,?57?7293) Schmarda?et al.?(2000)?The gastric H,K-ATPase blocker Iansoprazole is an inhibitor of chloride channels; Br. J. Pharmacol.,?129?5984) Maejima?et al.?(2020),?Oral oxytocin delivery with proton pump inhibitor pretreatment decreases food intake; Peptides,?128?1703125) Wantanabe?et al.?(2020),?Selective Targeting of Virus Replication by Proton Pump Inhibitors; Sci. Rep.,?10?40036) Bojkova?et al.?(2020),?SARS-CoV2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles;?bioRxiv, epub ahead of print?DOI: 10.1101/2020.04.03.024257
Check Digit Verification of cas no
The CAS Registry Mumber 73590-58-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,3,5,9 and 0 respectively; the second part has 2 digits, 5 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 73590-58:
(7*7)+(6*3)+(5*5)+(4*9)+(3*0)+(2*5)+(1*8)=146
146 % 10 = 6
So 73590-58-6 is a valid CAS Registry Number.
InChI:InChI=1/C17H19N3O3S/c1-10-8-18-15(11(2)16(10)23-4)9-24(21)17-19-13-6-5-12(22-3)7-14(13)20-17/h5-8H,9H2,1-4H3,(H,19,20)
73590-58-6Relevant articles and documents
Monitoring and Quantification of Omeprazole Synthesis Reaction by In-Line Raman Spectroscopy and Characterization of the Reaction Components
?ahni?, Damir,Me?trovi?, Ernest,Jedna?ak, Tomislav,Habinovec, Iva,Parlov Vukovi?, Jelena,Novak, Predrag
, p. 2092 - 2099 (2016)
The development of a quantitative in-line Raman spectroscopic method for the monitoring of the active pharmaceutical ingredient, omeprazole synthesis reaction, and characterization of the reaction components is described. In-line monitoring was performed both with Fourier transform and dispersive Raman spectrometers. Prior to reaction monitoring, the reaction components were characterized off-line by means of Raman and NMR spectroscopy, both in solution and in solid state. To unequivocally confirm the presence of each component in the reaction mixture, a state of the art LC-SPE/NMR methodology was also used. Owing to its higher sensitivity, dispersive Raman spectroscopy was further employed for quantification purposes. The spectroscopic measurements and the complementary HPLC analyses, used in the calibration development, were gathered from a set of experiments, performed at a 1 L scale. On the basis of the data set obtained from the calibration experiments, a predictive partial least-squares (PLS) regression model was developed for all three reaction components, enabling an accurate determination of the percentage of each component present in the reaction mixture, at any time after the point when 25% of the starting material has been consumed. The model was successfully used to monitor the reaction progress in a kilo-lab scale experiment and can further be used as a fast response analytical tool in process optimization. It also has the potential to be used as part of a feedback control loop in the production plant.
A mild and chemoselective CALB biocatalysed synthesis of sulfoxides exploiting the dual role of AcOEt as solvent and reagent
Anselmi, Silvia,Liu, Siyu,Kim, Seong-Heun,Barry, Sarah M.,Moody, Thomas S.,Castagnolo, Daniele
supporting information, p. 156 - 161 (2021/01/14)
A mild, chemoselective and sustainable biocatalysed synthesis of sulfoxides has been developed exploiting CALB and using AcOEt with a dual role of more environmentally friendly reaction solvent and enzyme substrate. A series of sulfoxides, including the drug omeprazole, have been synthesised in high yields and with excellent E-factors.
Preparation method of omeprazole and omeprazole
-
Paragraph 0049-0084, (2021/04/21)
The invention is applicable to the technical field of medicines, and provides a preparation method of omeprazole and omeprazole, and the preparation method comprises the following steps: dropwise adding a catalyst solution containing ammonium molybdate and hydrogen peroxide into a methanol solution of a thioether intermediate in sequence, and controlling the oxidation reaction temperature to -5-10 DEG C for reaction to obtain an omeprazole reaction solution; and adding sodium sulfite and a sodium hydroxide aqueous solution into the omeprazole reaction solution, uniformly mixing, dropwise adding an acetic acid aqueous solution, adding omeprazole seed crystals, stirring, continuously dropwise adding the acetic acid aqueous solution to adjust the pH value to 7.0-9.0, and adjusting the crystallization endpoint temperature to 10-20 DEG C, thereby obtaining the omeprazole crystal. The one-pot method of reaction and refining in the same solvent system is adopted, convenience of production operation is remarkably improved, operation steps are reduced, production energy consumption and time cost are reduced, and in addition, by optimizing all key parameters, the high-yield and high-purity omeprazole preparation process is achieved. The total yield of 25kg-grade production and preparation reaches 91.1%, the purity is 99.99%, and the method is superior to the pharmacopeia standard.
