ボセプレビル 化学特性,用途語,生産方法
効能
抗ウイルス薬, プロテアーゼ阻害薬
説明
In May 2011, the U.S. FDA approved boceprevir (SCH-503034), to be
given in combination with peginterferon alfa plus ribavirin, for the treatment
of patients with chronic hepatitis C genotype 1 viral infection.
Boceprevir and telaprevir are the first hepatitis C virus (HCV)
protease inhibitors to be approved for the treatment of HCV infection.
Boceprevir is an inhibitor of HCV NS3-4A protease, an essential enzyme required by HCV for
posttranslational processing of viral proteins into their mature forms.
Boceprevir binds covalently, but reversibly, to the active site serine by addition
of the hydroxyl group to the keto-amide functionality. Boceprevir
inhibits HCV NS3-4A protease with a Ki of 14 nM. In cell culture, the EC
50
of boceprevir was 200 nM for an HCV replicon constructed from genotype
1b. Boceprevir was two-to threefold less potent against HCV replicon from
genotypes 1a, 2, and 3. The potency of boceprevir decreased threefold in the
presence of human serum. Boceprevir was discovered through a series of
systematic truncations and modifications of a keto-amide undecapeptide
lead molecule.
Boceprevir is synthesized by coupling of 3-amino-4-
cyclobutyl-2-hydroxybutyramide or the related oxobutyramide with a
cyclopropyl-pyrrolidine carboxylic acid intermediate. The pyrrolidine derivative
can be prepared via cyclopropanation of a bicyclic lactam derivative
or by conversion of 3,3-dimethylcyclopropane-1,2-dicarboxylic acid to the
pyrrolidine in a multistep route. Boceprevir is a 1:1 mixture of diastereomers
at the readily epimerizable position a to the keto group.
化学的特性
Off-White to Pale Yellow Solid
使用
An NS3 serine protease inhibitor of hepatitis C virus, for the treatment of HCV infection. It is a COVID19-related research product.
定義
ChEBI: A synthetic tripeptide consisting of N-(tert-butylcarbamoyl)-3-methyl-L-valyl, a cyclopropyl-fused prolyl and 3-amino-4-cyclobutyl-2-oxobutanamide residues joined in sequence. Used for treatment of chronic h
patitis C virus genotype 1 infection.
臨床応用
Boceprevir is an oral inhibitor of HCV NS3/4A protease for the
treatment of the chronic hepatitis C genotype infection. It is approved
as combination therapy with Peg-IFN-alpha and ribavarin
to treat adult patients with compensated liver diseasewhoare either
treatment naive or who have experienced prior failed therapy with
interferon and ribavarin. Boceprevir was initially discovered by
Schering-Plough and developed and marketed by Merck & Co. since
its acquisition of Schering-Plough in 2009. Several publications have
highlighted the discovery of this drug, which evolved from a potent
initial undecapeptide lead structure to boceprevir (VII) as a drug
candidate with potent activity and desirable PK properties.
ボセプレビル 上流と下流の製品情報
原材料
Cyclobutanebutanoic acid, β-[[(1,1-dimethylethoxy)carbonyl]amino]-α-hydroxy-
N-メチルモルホリン塩酸塩
TERT-BUTYL 1-CYANO-3-CYCLOBUTYL-1-HYDROXYPROPAN-2-YLCARBAMATE
シクロブチルメチルブロミド
ボセプレビル代謝産物M4
2-((TERT-ブチルトキシカルボニル)アミノ)-3-シクロブチルプロパン酸
1025799-39-6
Ethyl 2-amino-3-cyclobutylpropanoate
3-アミノ-4-シクロブチル-2-オキソブタンアミド塩酸塩
3-Azabicyclo[3.1.0]hexane-2-carboxaMide, N-[3-aMino-1-(cyclobutylMethyl)-2-hydroxy-3-oxopropyl]-3-[(2S)-2-[[[(1,1 -diMethylethyl)aMino]carbonyl]aMino]-3,3-diMethyl-1-oxobutyl]-6,6-diMe thyl-, (1R,2S,5S)-
N-[1-(シクロブチルメチル)-2-(メトキシメチルアミノ)-2-オキソエチル]-カルバミン酸1,1-ジメチルエチルエステル
(1-シクロブチル-3-オキソプロパン-2-イル)カルバミン酸TERT-ブチル
Ethyl 2-(tert-butoxycarbonylamino)-3-cyclobutylpropanoate
準備製品