Ring-Closing Metathesis on Commercial Scale: Synthesis of HCV Protease Inhibitor Simeprevir

Horváth, András; Depré, Dominique; Vermeulen, Wim A. A.; Wuyts, Stijn; Harutyunyan, Syuzanna R.; Binot, Grégori; Cuypers, Jef; Couck, Wouter; Heuvel, Dirk van den

doi:10.1021/acs.joc.8b03124

Cited by 17 publications

(12 citation statements)

References 28 publications

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“…Simeprevir sodium (sodium; cyclopropylsulfonyl-[(1R,4R,6S,7Z,15R,17R)-17-[7-methoxy-8-methyl-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl]azanide) ( Table 2 ) – a small molecular drug targeting the NS3/4A protease of HCV was approved by FDA in 2013 as a component of Olysio™, for the treatment of chronic hepatitis C (CHC) infection [ 92 ]. Chemical work on the industrial-scale synthesis of this drug using ring-closing metathesis [ 122 ], for example, is still in progress.…”

Section: Molecular Mechanisms Of Action Of Non-nucleoside Structured Compoundsmentioning

confidence: 99%

Non-nucleoside structured compounds with antiviral activity—past 10 years (2010–2020)

Denel-Bobrowska

Olejniczak

2022

European Journal of Medicinal Chemistry

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Nucleosides and their derivatives are a well-known and well-described class of compounds with antiviral activity. Currently, in the era of the COVID-19 pandemic, scientists are also looking for compounds not related to nucleosides with antiviral properties. This review aims to provide an overview of selected synthetic antiviral agents not associated to nucleosides developed against human viruses and introduced to preclinical and clinical trials as well as drugs approved for antiviral therapy over the last 10 years. The article describes for the first time the wide classification of such antiviral drugs and drug candidates and briefly summarizes the biological target and clinical applications of the compounds. The described compounds are arranged according to the antiviral mechanism of action. Knowledge of the drug's activity toward specific molecular targets may be the key to researching new antiviral compounds and repositioning drugs already approved for clinical use. The paper also briefly discusses the future directions of antiviral therapy. The described examples of antiviral compounds can be helpful for further drug development.

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Section: Molecular Mechanisms Of Action Of Non-nucleoside Structured Compoundsmentioning

confidence: 99%

Non-nucleoside structured compounds with antiviral activity—past 10 years (2010–2020)

Denel-Bobrowska

Olejniczak

2022

European Journal of Medicinal Chemistry

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“…[106] In summary, the researchers at Boehringer Ingelheim put al ot of effort into optimizating the RCM process,n ot only focusing on practical issues but, importantly,u nderstanding its reaction mechanism and kinetics. [107] Thus,s ynthetic strategies optimized for Ciluprevir,s uch as controlling the effective molarity with N-protecting groups,w ork not only in closely related cases,such as the formation of the macrocyclic core of BI201302, [108] but were also useful in RCM leading to less related APIs,s uch as Simeprevir [109] and others.…”

Section: Applications In the Synthesis Of Active Pharmaceutic Ingredientsmentioning

confidence: 99%

Nitro and Other Electron Withdrawing Group Activated Ruthenium Catalysts for Olefin Metathesis Reactions

Kajetanowicz

Grela

2020

Angew Chem Int Ed

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From the Contents 1. Olefin Metathesis Reaction and Established Catalysts Types 13739 2. The EWG-Activation Concept, Early Observations, and Consequences 13740 3. Synthesis of Advanced Biologically Active and Natural Compounds by Utilizing EWG-Activated Catalysts 13741 4. Applications in the Synthesis of Active Pharmaceutic Ingredients 13748 5. Production of Specialty Chemicals and Commodities, as well as Applications in Materials Science 13750 6. Practical Considerations, Outlook, and Perspectives 13752 Scheme 1. Basic types of olefin metathesis. RCM = ring-closing metathesis;ROM = ring-opening metathesis;ADMET = acyclic diene metathesis;ROMP = ring-opening metathesis polymerization;C M= crossmetathesis.

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“…Insgesamt betrieben die Wissenschaftler von Boehringer Ingelheim einen hohen Aufwand zur Optimierung des RCM‐Prozesses, konzentrierten sich dabei allerdings nicht nur auf praktische Aspekte, sondern auch auf das Verständnis des Mechanismus und der Kinetik [107] . Die für Ciluprevir optimierten Syntheseverfahren, wie die Regulierung der effektiven Molarität über eine N‐Schutzgruppe, eigneten sich nicht nur für strukturell ähnliche Fälle wie die Bildung des makrozyklischen Kerns von BI201302, [108] sondern ließen sich auch auf entferntere APIs wie Simeprevir [109] und einige weitere anwenden.…”

Section: Anwendungen In Der Synthese Aktiver Pharmazeutischer Wirkstoffe (Apis)unclassified

“…Aufsätze dern ließen sich auch auf entferntere APIs wie Simeprevir [109] und einige weitere anwenden.…”

Section: Angewandte Chemieunclassified

Durch Nitro‐ und andere elektronenziehende Gruppen aktivierte Ruthenium‐Katalysatoren für die Olefinmetathese

Kajetanowicz¹,

Grela

2020

Angewandte Chemie

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Fortschrittliche Anwendungen der mit dem Nobelpreis ausgezeichneten Olefinmetathese erfordern nutzerfreundliche Handhabung und vielseitig anwendbare Katalysatoren. Unter den zahlreichen bekannten Metathesekatalysatoren, welche zu den zwei Klassen der Schrock‐ und Grubbs‐Katalysatoren gehören, bietet die Untergruppe der chelatisierten Rutheniumbenzyliden‐Komplexe (auch genannt Hoveyda‐Grubbs‐Katalysatoren) durch zusätzliche Aktivierung durch elektronenziehende Gruppen (EWG) eine hochgradig abstimmbare Plattform. Im vorliegenden Aufsatz werden der Ursprung des EWG‐Aktivierungskonzeptes und ausgewählte Anwendungen der resultierenden Katalysatoren in zielgerichteten Synthesen, im Bereich der medizinischen Chemie sowie in der Herstellung von Feinchemikalien und der Materialchemie erörtert. Darauf basierend werden dem Anwender einige Vorschläge hinsichtlich der Minimierung der Katalysatorbeladung, der Selektivitätskontrolle und allgemeine Optimierungshinweise der Olefinmetathese gegeben.

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Ring-Closing Metathesis on Commercial Scale: Synthesis of HCV Protease Inhibitor Simeprevir

Cited by 17 publications

References 28 publications

Non-nucleoside structured compounds with antiviral activity—past 10 years (2010–2020)

Non-nucleoside structured compounds with antiviral activity—past 10 years (2010–2020)

Nitro and Other Electron Withdrawing Group Activated Ruthenium Catalysts for Olefin Metathesis Reactions

Durch Nitro‐ und andere elektronenziehende Gruppen aktivierte Ruthenium‐Katalysatoren für die Olefinmetathese

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