AstraZeneca omeprazole

AstraZeneca launched omeprazole in 1988. It is a safe and effective drug for acid reflux, functioning as a proton pump inhibitor. However, the patent has expired and AstraZeneca has to compete against generics. The company developed the active isomer and called it esomeprazole. It was approved by the Mutual Recognition process in Europe in July 2000, and by the US Food and Drug Administration in February 2001. The chemical formulas for omeprazole and esomeprazole are shown below. 

The AstraZeneca patent on omeprazole expired in October 2001. AstraZeneca went to court to seek extended patent protection for a special formulation of omeprazole. The special formulation consists of a subcoating layer inserted between the core of the drug s active ingredient and the outer coating. The subcoating is formulated to protect the drug from being broken down quickly by the harsh acids in the stomach. 

USAN Omeprazole Trade Name. Prilosec AstraZeneca Launched 1985 M.W. 345 21... 

AstraZeneca (formerly Astra) has launched the proton-pump inhibitor esomeprazole (19) (as Nexium) as a treatment for peptic ulcer, gastroesophageal reflux disease, duodenal ulcer, and esophagitis. Esomeprazole is the (S)-enantiomer of omeprazole and was developed as a result of its improved pharmokinetic profile and better potency after oral dosing than (f )-form of omeprazole or the racemate. The dosage is higher than would be expected for a simple chiral switch. The stereogenic center is at sulfur. Detailed accounts of the development of the process have been published.189190... 

There are currently four racemic PPIs available on the market omeprazole, lansoprazole, pantoprazole, and rabeprazole. (More recently, enantiomerically pure versions have also been studied and developed, e.g., S-omeprazole, marketed by AstraZeneca as esomeprazole see Chapter II-2.) Proton pump inhibitors share the same core structure, the substituted pyridylmethyl-sulfmyl-benzimidazole, but differ in terms of substituents on this core structure. The absolute requirements of the core structure for the activity of PPIs was not understood until it became clear that the active PPIs are derived from inactive prodrugs the prodrugs are transformed, in the acid-secreting parietal cells, by a unique cascade of chemical structural transformations leading to the active principle, a cyclic sulfenamide species. Inhibition of acid secretion in turn is then achieved by formation of covalent disulfide bonds with key cysteines of the (H+/K+)-ATPase. 

Ranitidine (Zantac /GlaxoSmithKline) is a histamine H2-receptor antagonist that inhibits the release of gastric acid and is useful in the treatment of a variety of hypersecretory conditions [dyspepsia, heartburn, duodenal and gastric ulcers, and gastroesophageal reflux (GERD)]. Lansoprazole (Prevacid /TAP), omeprazole (Prilosec /AstraZeneca), and esomeprazole (Nexium /AstraZeneca) are benzimidazole... 

In the area of metal catalyzed asymmetric sulfoxidation there is still much room for improvement. The most successful examples involve titanium tartrates, but at the same time often require near stoichiometric quantities of catalysts [301, 302]. Recently, this methodology has been successfully used for the production of (S)-Omeprazole by AstraZeneca [303] (see Fig. 4.110). A modified Kagan-pro-cedure [302] was applied, using cumene hydroperoxide as the oxidant. Another example is the sulfoxidation of an aryl ethyl sulfide, which was in development by Astra Zeneca as a candidate drug for the treatment of schizophrenia. In this case the final ee could be improved from 60% to 80% by optimising the Ti tar-trate ratio [304]. 

The recently launched Esomeprazole (97, AstraZeneca), which is the (5)-isomer of the anti-ulcer drug. Omeprazole (a typical racemic switch agent) is effectively synthesized by employing diethyl tartrate (DET), titanium tetraisopropoxide, and cumene hydroperoxide with > 90 % yield and > 90 % ee (Scheme 29) [89]. Under optimal conditions an amazing cost performance is realized to produce Esomeprazole cheaper than the racemic Omeprazole [89b]. 

Omeprazole Losec AstraZeneca Proton-pump inhibitor... 

Omeprazole (Prilosec, AstraZeneca) is a drug termed as proton pump inhibitor. It turns off the secretions of acid into the stomach. When less acid is produced, there is a reduced amount of acid that can flow back up from the stomach into the esophagus to cause reflux symptoms. 

Omeprazole (Losec, AstraZeneca) proton pump inhibitor for the prevention of relapse in reflux esophagitis... 

Omeprazole (Losec) Bupivacaine (Sensorcaine) Ketoprofen (Orudis) Ofloxacin (Floxin) Cetirizine.HCl (Zyrtec) AstraZeneca AstraZeneca Wyeth Ortho-McNeil Pfizer Esomeprazole (Nexium) Levobupivacaine (Chirocaine) Dexketoprofen (Enantyum) Levofloxacin (Levaquine) Levocetirizine (Xyzal) AstraZeneca Chirosdence Menarini Ortho-McNeil Sepracor... 

The pyridine ring is found in many current pharmaceuticals. It is present in some proton pump inhibitors used for reducing the amount of acid produced by the stomach. These dmgs can be used to treat reflux disease, ulcers, or heartburn. Omeprazole is sold by AstraZeneca Pharmaceuticals LP as the magnesium salt in the racemic form as PRILOSEC and as the S enantiomer as NEXIUM. Lansoprazole is sold by TAP Pharmaceuticals Inc. as PREVACID. Pantoprazole is sold by Wyeth Pharmaceuticals Inc. as the sodium salt under the name PROTONIX. Rabeprazole was developed by Eisai Co. Ltd., who sells it as the sodium salt under the name ACIPHEX. Each of these also contains a benzimidazole ring. 

Losec (2apsules (Omeprazole). AstraZeneca UK Limited. UK Summary of product characteristics, July 2006. 

Prilosec (Omeprazole delayed-release). AstraZeneca. US Prescribing infmnation, April 2007. 

One prominent example is AstraZeneca s H /K -ATPase inhibitor, pyridine-containing omeprazole (Prilosec) and its enantiomerically pure follow-up esomeprazole (Nexium). 

Esomeprazole (AstraZeneca). Esomeprazole is the (iS)-enantiomer of Omeprazole, the best selling antiulcer compound, and will be produced on a multitons per year scale. The key step of the new synthesis is the Ti-catalyzed oxidation of the sulfide intermediate (27b,47b,48,49). 

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