タミフル

外観

白色～ごくうすい黄色、結晶性粉末～粉末又は塊

溶解性

水に可溶

医薬用

タミフルは，A型およびB型インフルエンザ感染症に対する経口抗インフルエンザウイルス薬の製品名。一般名はリン酸オセルタミビル。［幸保文治］[参照項目] | リン酸オセルタミビル
小学館　日本大百科全書(ニッポニカ) ）

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。

効能

抗ウイルス薬, ノイラミニダーゼ阻害薬

商品名

タミフル (中外製薬); タミフル (中外製薬)

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.

化学的特性

White Cyrstalline Solid. It is freely soluble in water.

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

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/jo3015853

It can also be obtained by a novel 12-step synthesis from (-)-quinic acid.

定義

ChEBI: Oseltamivir phosphate is a phosphate salt. It contains an oseltamivir. It is an acetamido cyclohexene that is a structural homolog of SIALIC ACID and inhibits NEURAMINIDASE.

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.

臨床応用

Oseltamivir was approved as the first orally administered neuraminidase inhibitor used against influenza A and B viruses. The drug is indicated for the treatment of uncomplicated acute illness caused by influenza infection.

副作用

Side effects with oseltamivir are minor, consist of nausea and vomiting, and occur primarily in the first two days of therapy.

代謝

Oseltamivir is readily absorbed from the GI tract following oral administration. It is a prodrug that is extensively metabolized in the liver, undergoing ester hydrolysis to the active carboxylic acid. Two oxidative metabolites also have been isolated, with the major oxidation product being the ω-carboxylic acid.

Mode of action

Oseltamivir Phosphate is the phosphate salt of oseltamivir, a synthetic derivative prodrug of ethyl ester with antiviral activity. By blocking neuraminidases on the surfaces of influenza viruses, oseltamivir interferes with host cell release of complete viral particles.