タミフル

用途ノイラミニダーゼ阻害剤です。 代謝により活性体に変換され、インフルエン ザウイルスのノイラミニダーゼを阻害し、新 たに形成されたウイルスの細胞外への遊離を 阻害することにより、ウイルスの増殖を抑制 します。

説明Oseltamivir phosphate (Tamiflu) was launched in the US and Switzerland for the treatment of influenza infections by all common strain viruses. It is an oral anti-viral drug approved for the treatment of acute, uncomplicated influenza in patients 2 weeks of age and older whose flu symptoms have not lasted more than two days. This product is approved to treat Type A and B influenza; however, the majority of patients included in the studies were infected with type A, the most common in the U.S. Efficacy of Tamiflu in the treatment of influenza in subjects with chronic cardiac disease and/or respiratory disease has not been established.

使用Oseltamivir phosphate (Tamiflu) is a competitive neuraminidase inhibitor. The prodrug oseltamivir phosphate (Tamiflu) is itself not virally effective; however, once in the liver, it is converted by natural chemical processes, hydrolysed hepatically to its

一般的な説明receptor site showed clearly that additional binding sitesexist for the C-5 acetamido carbonyl group and the arginineresidue at position 152 of the receptor site. In addition, the C-2 carboxyl group of sialic acid binds to Arg 118, Arg 292, andArg 371. Position C-6 is capable of undergoing a hydrophobicinteraction with various amino acids, including Glu, Ala,Arg, and Ile. Maximum binding to neuraminidase occurswhen the C-6 substituent is substituted with a nonpolar chain.In oseltamivir, this nonpolar group is 3-pentyl. An importantfeature of oseltamivir is the ethyl ester, which makes the drugorally efficacious. This drug is the first orally active agent foruse against influenza A and B. It is also indicated for the treatmentof acute illness. If administered within 2 days after theonset of influenza symptoms, the drug is effective.

製造方法Oseltamivir phosphate (Tamiflu) has been synthesized from cis-2,3-bis(hydroxymethyl)aziridine. After protection of the cis-2,3-bis(hydroxymethyl)aziridine with a Boc group, desymmetrization provided a chiral aziridine, which was a key intermediate to install the required stereogenic center containing a nitrogen atom. Allylation and ring closing metathesis are the key reactions to obtain the cyclic product that was successfully converted to the desired oseltamivir phosphate. DOI: 10.1021/jo3015853It can also be obtained by a novel 12-step synthesis from (-)-quinic acid.