Oseltamivir Tamiflu

New infectious diseases appear regularly in different parts of the globe, most recently swine flu, creating new global health threats. The appearance of new 

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Exhibit 3.7 Development of Zanamivir (Relenza) and Oseltamivir (Tamiflu)... 

Two drugs were designed zanamivir (Relenza) by Glaxo Wellcome and oseltamivir (Tamiflu) by Roche. Zanamivir is a powder that has to be inhaled, and oseltamivir is an oral drug. 

Imatinib mesylate (Gleevec, Novartis), zanamivir (Relenza, GlaxoSmithKline), and oseltamivir (Tamiflu, Roche) are examples of drugs (Exhibits 3.11 and 3.7) that show the successful contributions of rational drug design. For example, the X-ray structure of angiotensin converting enzyme (ACE) has been reported (see Exhibit 11.2), and this may pave the way for more effective ACE inhibitors to be developed for the treatment of hypertension and heart disorders. 

Corey, E. J. Kim, C. U. J. Am. Chem. Soc. 1972, 94, 7586. Choung U. Kim now works at Gilead Sciences Inc., a company specialized in antiviral drugs in Foster City, CaUfomia, where he co-discovered oseltamivir (Tamiflu). 

Oseltamivir (Tamiflu) Palivizumab (Synagis) Peg Interferon Alfa-2a (Pegsys)... 

A step in the synthesis of the antiviral drug (-)-oseltamivir (Tamiflu) was the conversion of an amide to an imide with RuO /aq. NaCIO VCH Cl [74],... 

The dataset used in this example comprised two phase III placebo-controlled studies used in the license application for oseltamivir (Tamiflu ). See Patel, Kay and Rowell (2006) for further details. Pre-defined symptoms consisted of cough, nasal congestion, headache, sore throat, fatigue, myalgia and feverishness and each of these was assessed on an ordinal scale none, mild, moderate, severe. Alleviation was recorded as the day on which all symptoms... 

Oseltamivir Tamiflu Prevention and treatment of influenza A and B infections... 

Antiviral Efficacy and Clinical Use. Oseltamivir (Tamiflu) and Zanamivir (Relenza) are effective against influenza virus types A and B. These drugs can reduce the duration and severity of flu symptoms if the drug is administered within 48 hours after symptoms first appear.22,46 These drugs can also be taken pro-phylactically to reduce the risk of getting the flu, especially in people who are at high risk (older adults, people with respiratory disorders), or in cases where an individual is exposed to a family member or someone else with the flu.3... 

Sullivan B, Carrera I et al (2009) Symmetry-based design for the chemoenzymatic synthesis of oseltamivir (tamiflu) from ethyl benzoate. Angew Chem Int Ed 48 4229 1231... 

Zanamivir (Relenza, 3.22) is used to fight the viruses that cause influenza A and influenza B (Figure 3.13). Because its oral bioavailability is low at only 2%, an alternative delivery route, inhalation, is required for zanamivir. As a possible demonstration of the public s general preference for oral drugs, oseltamivir (Tamiflu, 3.23), an oral influenza drug, far outsells the inhaled drug zanamivir. 

Only one oral influenza A antiviral has been approved for use in the United States. That drug, oseltamivir (Tamiflu, A.181), inhibits neuraminidase, a viral enzyme involved in the budding of new viruses from infected cells (Figure A.51). The only other oral drug is arbidol (A.182), a drug approved for use in Russia and China. Arbidol is believed to act as a fusion inhibitor and also may stimulate the body s immune response. 

Oseltamivir (Tamiflu) is derived from shikimic acid, itself extracted from various plant sources (e.g., Quinic acid ex the bark of various Cinchona trees and Shikimic acid ex the Star Anise plant). 

The discovery of oseltamivir (Tamiflu , Figure 30.2d), an inhibitor of influenza neuraminidase, is another early... 

FIGURE 30.2 The first marketed drugs derived from structure-based design, (a) captopril (Capoten ), (b) dorzolamide (Trusopt ), (c) zanamivir (Relenza ), and (d) oseltamivir (Tamiflu ). 

After the virus penetrates the cell membrane, another viral protein, neuraminidase (sialidase), cleaves the glycosidic bonds to the sialic acid residues, freeing the virus to infect the cell. Inhibitors of this enTiyme such as oseltamivir (Tamiflu) and zanamivir (Relenza) are important anti-influenza agents. 

Oseltamivir Tamiflu Gilead and Roche 1999 Neuraminidase Influenza 118 O... 

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