Ethyl ester prodrug

Pharmacology 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 via inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release. 

A second approach involving use of the ethyl ester prodrug ABT-667 (191) has proven more successful, with this compound currently in clinical studies. 

Fig. 1 The structure of the neuraminidase inhibitor Ro-64-0802 and its ethyl ester prodrug Oseltamivir.

Oseltamivir came on the market in 2000 under the name of Tamiflu 36, which is the phosphate salt of the ethyl ester prodrug [86]. Oseltamivir phosphate is well absorbed in the G1 tract and can therefore be administered orally. Approximately 80% of an oral dose reaches... 

Subsequently, GS4104 (the ethyl ester prodrug of GS4071) has found to be highly orally bioavailable in several animal species and efBcacious in both the mouse and ferret models of influenza infection by oral administration [48,49]. 

Canderel aspartame, candesartan candesartancilexetil. eandesartan cilexetil (Amias ) is a benzimidazole-carboxylic acid derivative, an (AT,) ANGIOTENSIN RECEPTOR ANTAGONIST, used as an antihypertensive. It is an ethyl ester prodrug of candesartan (CV 11974). It has experimental renal protective effects. 

Oseltamivir (GS 4104, 4a), developed by Gilead/Hoffmann-LaRoche and marketed as Tamiflu , is the first commercially available orally active, noncarbohydrate mimetic of Zanamivir (3) [49-51]. It is based on a cyclohexene framework with a lipophilic moiety replacing the glycerol side chain of Zanamivir (3). It is orally administered as an ethyl ester prodrug GS 4104 (4a), which—upon absorption in the gastrointestinal tract—undergoes rapid enzymatic conversion by the action of... 

Oseltamivir phosphate is an ethyl ester prodrug that lacks antiviral activity. Oseltamivir carboxylate has an antiviral spectrum and potency similar to that of zanamivir. It inhibits amantadine- and rimantadine-resistant influenza A viruses and some zanamivir-resistant variants. 

The ethyl ester prodrug form (7) of the amino derivative 6 was taken into clinical development by Hoffmann-La Roche (reviewed in [157]) imder the generic name oseltamivir. Oseltamivir gained regulatory approval from the FDA in the United States in 1999, under the tradename Tamiflu, for the treatment (75 mg, twice daily, for 5 days) and prevention of influenza, by oral administration. 

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. ... 

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