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テラプレビル-D4

テラプレビル-D4 化学構造式
402957-28-2
CAS番号.
402957-28-2
化学名:
テラプレビル-D4
别名:
テラプレビル-D4;テラプレビル;テラプレビル (JAN)
英語化学名:
Telaprevir
英語别名:
CS-61;VX-950;MP-424;CS-1855;Incivek;LY-570310;Telaprevir;tellaprevir;Telaprevir-d4;Telaprevir, >=98%
CBNumber:
CB41519837
化学式:
C36H53N7O6
分子量:
679.85
MOL File:
402957-28-2.mol

テラプレビル-D4 物理性質

比重(密度) :
1.25
酸解離定数(Pka):
11.84±0.20(Predicted)

安全性情報

Sフレーズ  24/25
HSコード  29339900

テラプレビル-D4 価格 もっと(4)

メーカー 製品番号 製品説明 CAS番号 包装 価格 更新時間 購入
富士フイルム和光純薬株式会社(wako) W01TRCT015652 テラプレビル-d4
Telaprevir-d4
402957-28-2 0.25mg ¥112500 2018-12-26 購入
富士フイルム和光純薬株式会社(wako) W01MAS122741 テラプレビル
Telaprevir
402957-28-2 1g ¥2613600 2018-12-26 購入
富士フイルム和光純薬株式会社(wako) W01TRCT015652 テラプレビル-d4
Telaprevir-d4
402957-28-2 1mg ¥437500 2018-12-26 購入
富士フイルム和光純薬株式会社(wako) W01TRCT015652 テラプレビル-d4
Telaprevir-d4
402957-28-2 5mg ¥1312500 2018-12-26 購入

テラプレビル-D4 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

The hepatitis C virus (HCV) protease inhibitor telaprevir (VX-950, MP- 424,LY-570310) was approved by the U.S. FDA in May 2011 for the treatment of genotype 1 chronic HCV infection in adult patients in combination with peginterferon alfa and ribavirin (PR). Telaprevir and boceprevir (vide supra) are the first two HCV protease inhibitors to be approved for treatment of HCV infection. Telaprevir is a HCV NS3-4A protease inhibitor that exerts its antiviral effect by blocking the release of nonstructural viral proteins from a polyprotein precursor. Telaprevir is a potent inhibitor of the protease (IC50=10 nM) and is active in cell culture (HCV 1b replicon assay, EC50=354 nM). Telaprevir was identified from efforts to truncate a decamer peptide inhibitor derived from the natural substrate NS5A-5B and was guided by structure-based design. The ketoamide group of telaprevir forms a covalent, reversible bond with the active site serine hydroxyl of the protease and compensates for the loss of affinity resulting from truncation of the peptide. Despite the presence of the reactive keto-amide group, telaprevir is >500-fold less potent against other serine proteases. Synthesis of the key octahydrocyclopenta[c]pyrrole-1-carboxylic acid fragment of telaprevir is achieved by a-deprotonation of Boc-protected 3-azabicyclo[3.3.0]nonane followed by reaction with CO2 and resolution of the racemic acid. Alternatively, deprotonation is carried out in the presence of a chiral amine to give the enantiomerically enriched acid.

化学的特性

Telaprevir is White Solid

Originator

Eli Lilly (United States)

使用

Telaprevir is a peptidomimetic inhibitor of hepatitis C virus protease.

使用

Labeled Telaprevir, intended for use as an internal standard for the quantification of Telaprevir by GC- or LC-mass spectrometry.

使用

A labelled peptidomimetic inhibitor of hepatitis C virus protease.

定義

ChEBI: An oligopeptide consisting of N-(pyrazin-2-ylcarbonyl)cyclohexylalanyl, 3-methylvalyl, octahydrocyclopenta[c]pyrrole-1-carboxy, and 3-amino-N-cyclopropyl-2-oxohexanamide residues joined in sequence. Used f r treatment of chronic hepatitis C virus genotype 1 infection.

brand name

Incivek

臨床応用

Telaprevir is a potent peptide mimetic inhibitor of Hepatitis C virus (HCV) and works via covalent reversible binding to the NSV-3A protease enzyme. Telaprevir was discovered and developed by Vertex pharmaceuticals. The drug is marketed as an oral treatment for HCV infection in combination with Peg interferon and ribavarin for patients who are refractory to the initial standard therapy. The initial SAR studies and the discovery of teleprevir have been published. In addition, a full review of the discovery process that led to the development of telaprevir, including several iterations of the syntheses of teleprevir leading to the process route, has been reported.

Chemical Synthesis

For preparation of bulk API, a convergent synthetic strategy was utilized as described in the scheme. Retrosynthetically the penultimate intermediate 212, which was coupled with amine 213 for the final step, was prepared by coupling bicyclic amine 217 with amino acids 216 and 215 and then with pyrazine acid 214.
In the early stages of development, the cyclopropyl amide fragment 213 was made using a MCR coupling sequence by reacting aldehyde 218 with cyclopropyl isocyanide (219) and triflouroacetic acid to give amide alcohol 220 in 85% yield. Removal of the Cbz group was accomplished via hydrogenolysis to provide key cyclopropyl amide alcohol 213 in 95% yield. While this route was shorter in terms of steps, it was not amenable to large-scale preparation due to difficulties associated with the handling of isocyanide 219.


Thus, for large-scale synthesis, the route depicted in Scheme 35 was utilized. Commercially available Cbz-protected amino acid 221 was converted to the corresponding Weinreb amide 222 using CDI as the activating agent. This was followed by LAH reduction to give aldehyde 218 in 73% yield from 221. Aldehyde 218 was reacted with sodium cyanide under neutral to mildly basic conditions allowing for easy workup of the cyanohydrin, which was immediately hydrolyzed by refluxing in 4 N hydrochloric acid in dioxane to deliver hydroxy acid HCl salt 223. Since the formation of the acyloin resulted in removal of the Cbz protecting group, reinstallation of this protecting group preceded conventional amide bond formation through the intermediacy of the succinate ester of 224. This provided the desired amide alcohol 220 in 56% yield from 223. Hydrogenolysis of Cbz carbamate 220 then furnished the requisite intermediate amine (213) in 73% yield.
The large-scale synthesis of bicyclic pyrrolidine 231 was accomplished as described in the following scheme. Commercially available 3-azabicyclo[ 3.3.0]nonane hydrochloride (225) was first protected as the corresponding Boc carbamate 226 in 90% yield. Deprotonation of the bicyclic pyrrolidine carbamate 226 with sec-BuLi and sequential quench with bubbling carbon dioxide gas followed by sodium hydrogensulfate resulted in racemic acid 227 in 80% yield. Racemate 227 was resolved using (S)-tetrahydronapthalamine (228) in ethyl acetate and isopropanol at 70–75°C. This mixture was allowed to cool down slowly to effect the crystallization of the optically enriched chiral salt 229 in 83% yield with greater than 99.5% ee. This enatioenriched salt was free based with sodium hydrogen sulfate and converted to t-butyl ester 230 using Boc anhydride and DMAP. The secondary amine of 230 was liberated using methane sulfonic acid at room temperature followed by salt formation with oxalic acid in isopropyl acetate to give oxalic acid salt 231 in 81% yield over 3 steps.
With the synthesis of the key intermediates complete, sequential coupling events were then executed to complete the synthesis of teleprevir (following scheme). Fragment 217 was coupled with the Cbz-protected valine (216) using EDCI and HOBt to give intermediate 232 in 87% yield. Similarly, after removal of the Cbz group of 232 via catalytic hydrogenolysis, the resulting amine was coupled with cyclohexyl amino acid 215 to give dipeptide intermediate 233 in 89% yield over 2 steps. Sequential cleavage of the Cbz group in 233 followed by CDI-mediated coupling with commercially available pyrazine acid 214 gave rise to the expected pyrazine amide intermediate. Subsequent hydrolysis of the t-butyl ester through the use of concentrated acid in DCM provided the key intermediate tripeptidic acid (212) in 68% over 3 steps. The tripeptide 212 was then coupled with cyclopropyl amide amine 213 using EDCI, HOBt and N-methyl morpholine (NMM) to provide penultimate intermediate alcohol 234 in 95% yield. Subjection of 234 to Dess–Martin periodinane (DMP) oxidation in t-butanol and DCM furnished telaprevir (XXI) in 85% yield.

テラプレビル-D4 上流と下流の製品情報

原材料

準備製品


テラプレビル-D4 生産企業

Global( 229)Suppliers
名前 電話番号 ファックス番号 電子メール 国籍 製品カタログ 優位度
Alpha Biopharmaceuticals Co., Ltd
0086-411-39042497
0086-411-39042693 sales@alphabiopharm.com China 896 58
Capot Chemical Co.,Ltd.
+86(0)13336195806 +86-571-85586718
+86-571-85864795 sales@capotchem.com China 20010 60
Henan DaKen Chemical CO.,LTD.
+86-371-55531817
info@dakenchem.com CHINA 21552 58
Beijing Cooperate Pharmaceutical Co.,Ltd
010-60279497
010-60279497 sales01@cooperate-pharm.com CHINA 1817 55
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com CHINA 22609 55
Hangzhou FandaChem Co.,Ltd.
008615858145714
+86-571-56059825 fandachem@gmail.com CHINA 8874 55
Shanghai Yingrui Biopharma Co., Ltd.
+86-21-33585366 E-mail:sales03@shyrchem.com
+86-21-34979012 sales03@shyrchem.com CHINA 739 60
ATK CHEMICAL COMPANY LIMITED
+86 21 5161 9050/ 5187 7795
+86 21 5161 9052/ 5187 7796 ivan@atkchemical.com CHINA 26699 60
career henan chemical co
+86-371-86658258
sales@coreychem.com CHINA 29992 58
Biochempartner
0086-13720134139
candy@biochempartner.com CHINA 968 58

402957-28-2(テラプレビル-D4)キーワード:


  • 402957-28-2
  • (1S,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxaMido)acetaMido)-3,3-diMethylbutanoyl)-N-((S)-1-(cyclopropylaMino)-1,2-dioxohexan-3-yl)octahydrocyclopenta[c]pyrrole-1-carboxaMide
  • Cyclopenta(c)pyrrole-1-carboxamide, (2S)-2-cyclohexyl-N-(pyrazinylcarbonyl)glycyl-3-methyl-L-valyl-N-((1S)-1-((cyclopropylamino)oxoacetyl)butyl)octahydro-, (1S,3aR,6aS)-
  • VX-950
  • VX-950 (Teleprevir)
  • (1S,3aR,6aS)-(2S)-2-Cyclohexyl-N-(pyrazinylcarbonyl)glycyl-3-methyl-L-valyl-N-((1S)-1-((cyclopropylamino)oxoacetyl)butyl)octahydrocyclopenta[c]pyrrole-1-carboxamide
  • Telaprevir
  • (1S,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-6-carboxamido)acetamido)-3,3-dimethylbutanoyl)-N-((S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl)-octahydrocyclopenta[c]pyrrole-1-carboxamide VX-950
  • TELAPREVIR; VX-950
  • VX-950(Telaprevir)
  • LY-570310
  • MP-424
  • (1S,3aR,6aS)-(2S)-2-Cyclohexyl-N-(pyrazinylcarbonyl)glycyl-3-methyl-L-valyl-N-((1S)-1-((cyclopropylamino)oxoacetyl)butyl)octahydrocyclopenta[c]pyrrole-1-carboxamide Telaprevir(VX950)
  • (1S,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxaMido)acetaMido)-3,3-diMethylbutanoyl)-N-((R)-1-(cyclopropylaMino)-1,2-dioxohexan-3-yl)octahydrocyclopenta[c]pyrrole-1-carboxaMid
  • telaprevir (VX-950) (Incivek)
  • Cyclopenta(c)pyrrole-1-carboxamide, (2S)-2-cyclohexyl-N-(pyrazinylcarbonyl)glycyl-3-methyl-L-valyl-N
  • Telaprevir (1S,3aR,6aS)-(2S)-2-Cyclohexyl-N-(pyrazinylcarbonyl)glycyl-3-methyl-L-valyl-N-((1S)-1-((cyclopropylamino)oxoacetyl)butyl)octahydrocyclopenta[c]pyrrole-1-carboxamide
  • Telaprevir-d4
  • Telaprevir, >=98%
  • tellaprevir
  • (1S,3aR,6aS)-N-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)-N-((S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl)octahydrocyclopenta[c]pyrrole-1-carboxamide
  • Cyclopenta(c)pyrrole-1-carboxamide
  • Telaprevir intermediates
  • Telaprevir, 98%, Hepatitis c virus (HCV)NS3-4Aserine protease inhibitors
  • (1S,3aR,6aS)-(2S)-2-Cyclohexyl-N-(2-pyrazinylcarbonyl)glycyl-3-methyl-L-valyl-N-[(1S)-1-[2-(cyclopropylamino)-2-oxoacetyl]butyl]octahydrocyclopenta[c]pyrrole-1-carboxamide
  • CS-1855
  • CS-61
  • VX950;TELAPREVIR;VX 950
  • Incivek
  • (1S,3AR,6AS)-2-((S)-2-((S)-2-CYCLOHEXYL-2-(PYRAZINE-6-CARBOXAMIDO)ACETAMIDO)-3,3-DIMETHYLBUTANOYL)-N-((S)-1-(CYCLOPROPYLAMINO)-1,2-DIOXOHEXAN-3-YL)-OCTAHYDROCYCLOPENTA[C]PYRROLE-1-CARBOXAMIDE
  • Cyclopenta[c]pyrrole-1-carboxamide, (2S)-2-cyclohexyl-N-(2-pyrazinylcarbonyl)glycyl-3-methyl-L-valyl-N-[(1S)-1-[2-(cyclopropylamino)-2-oxoacetyl]butyl]octahydro-, (1S,3aR,6aS)-
  • テラプレビル-D4
  • テラプレビル
  • テラプレビル (JAN)
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