Antiviral drugs Tamiflu

The main component (80-90%) is (f )-anethole. Star anise oil and (F)-anelhole isolated from it are used in anise liqueur (Anisette, Sambuca) and anise brandy (Pernod, Ouzo, Raki, Arak), liquorice sweets, toothpaste, etc. It has almost completely replaced the original anise seed oil, obtained from the umbellifer P. anisum. Shikimic acid (Wang et al., 2001), used in the production of the antiviral drug Tamiflu (Roche), is extracted from the fruits of Chinese star anise and related species (Rahway, 1989). 

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). 

Two ciT-dihydroxylation reactions of alkenes formed steps in the synthesis of the antiviral drug (-)-oseltamvir ( tamiflu ) were carried out with RuO /aq. Na(IO )/ EtOAc-CH3CN/4°C [169]. Terminal alkene groups in nucleosides were oxidised to alcohols by RuClj/aq. Na(lO )/EtOAc-CH3CN/0°C thus 3,5-di-0-benzyl-l,2-di-O-isopropylidene-3-C-vinyl-a-D-ribofuranose (1) gave the diol (2) which, on cleavage with Na(lO ) and reduction with NaBH yielded 3,5-di-0-benzyl-l,2-di-O-isopropylidene-3-C-hydroxy-methyl-a-D-ribofuranose (3) (Fig. 3.4) [170]. 

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],... 

ProbiGm 3.2 Tamiflu, the most effective antiviral drug against avian influenza currently available, can be prepared in 10 steps from shikimic acid. Identify the functional groups in Tamiflu and shikimic acid. 

Tamiflu is one of the few antiviral drugs currently available. It is used for the prevention and treatment of influenza A and B. Before a virus particle can be released from its host cell, an enzyme called neuraminidase must cleave off a sugar residue (N-acetylneuramic acid) from a glycoprotein on the surface of the cell (Section 21.18). Because N-acetylneuramic acid and Tamiflu have similar shapes, the enzyme cannot distinguish between them. Therefore, it can bind either one at its active site. When the enzyme binds Tamiflu, it cannot bind A-acetylneuramic acid. Thus, the virus particles are prevented from being released from their host cells, in which case they cannot infect new cells. Early treatment with Tamiflu is important because it will be less effective if a lot of cells have already been infected. In the past 10 years, 500 million people have been treated with Tamiflu. 

Every year we face an outbreak of influenza (the flu). Most of the time it is a virus that is already present in the population and therefore can be controlled by flu shots. But every once in awhile, a new influenza virus appears, which can cause a worldwide pandemic because it is not affected by any immunity a person may have to older strains of influenza and can therefore spread rapidly and infect a large number of people. And almost no effective antiviral drugs are available for the flu. (See Tamiflu on page 1124.)... 

Shikimic acid is the basis for the antiviral drug in Tamiflu. 

CI.15 Tamiflu (Oseltamivir), C15H28N2O4, is an antiviral drug used to treat influenza. The preparation of Tamiflu begins with the extraction of shikimic acid from the seedpods of star anise. From 2.6 g of star anise, 0.13 g of shikimic acid can be obtained and used to produce one capsule containing 75 mg of Tamiflu. The usual adult dosage for treatment of influenza is two capsules of Tamiflu daily for 5 days. (7.1, 7.2)... 

Oseltamivir is an antiviral drug whose phosphate salt is marketed by Hoffmann-La Roche (Basel, Switzerland) under the trade name Tamiflu sold as capsules containing 30 mg, 45 mg, or 75 mg oseltamivir for oral use. It is indicated for the treatment of uncomplicated acute infection caused by influenza A or B virus in patients older than 1 year of age who have been symptomatic for no more than 2 days. Oseltamivir is an ethyl ester prodrug requiring ester hydrolysis for conversion to the active form, oseltamivir carboxylate. The proposed mechanism of action of oseltamivir is inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release. ... 

Oseltamivir, better known as Tamiflu, is the antiviral worldwide employed for the treatment of influenza (flu). Due to the importance of that drug for treating regular seasonal flu and its potential use in the case of pandemic flu scenarios, it is... 

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... 

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. 

Influenza A viruses cause severe infections in the respiratory system and are responsible for seasonal epidemics and sporadic pandemics. The primary method for prevention is through vaccination but vaccine production by current methods cannot be carried out in time to stop the progress of a new strain of the influenza virus. Therefore, effective antiviral agents are used for prophylactic and therapeutic treatments. Among several viral molecular targets for anti-influenza drugs, the surface glycoprotein neuraminidase appears particularly attractive. Selective inhibitors of this enzyme have been developed and two of which, oseltamivir phosphate 18 (Tamiflu ) " and zanamivir 19 (Relenza ), have been approved for human use (Scheme 6). 

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