Abstract:Background
Rilpivirine (RPV) was approved by the U.S. FDA (Food and Drug Administration) in 2011 to treat individuals infected with human immunodeficiency virus 1 (HIV-1). Significantly, rilpivirine is three fold more potent than etravirine. Once-daily, it is used with a low oral dose (25 mg/tablet), decreasing the drug administration and bringing a better choice to the patients. However, there are many shortcomings in the existing synthesis route of RPV, such as the high cost, prolonged reacti… Show more
“…33 Both routes require the use of catalysts based on transition metals (e.g., Pd(OAc) 2 , P(oTol) 3 , and Pd/C), which are not ideal for industrial setups. 34 Our approach to access arylacrylonitriles through the RBR seemed ideal for the development of a transition metal-free formal synthesis of rilpivirine through the preparation of 3 (Scheme 2b). Masked benzylmercaptane 6 was obtained from aminoalcohol 5 by a thio-Mitsunobu reaction, followed by tandem acetyl cleavage/S-alkylation using chloroacetonitrile under basic media, and oxidation with Oxone® to deliver sulfone precursor 7.…”
The applicability of vinyl nitriles for the preparation of pharmaceuticals, polymers, and other valuable materials benefits from robust preparative methodologies. In this work, we present a novel approach for the...
“…33 Both routes require the use of catalysts based on transition metals (e.g., Pd(OAc) 2 , P(oTol) 3 , and Pd/C), which are not ideal for industrial setups. 34 Our approach to access arylacrylonitriles through the RBR seemed ideal for the development of a transition metal-free formal synthesis of rilpivirine through the preparation of 3 (Scheme 2b). Masked benzylmercaptane 6 was obtained from aminoalcohol 5 by a thio-Mitsunobu reaction, followed by tandem acetyl cleavage/S-alkylation using chloroacetonitrile under basic media, and oxidation with Oxone® to deliver sulfone precursor 7.…”
The applicability of vinyl nitriles for the preparation of pharmaceuticals, polymers, and other valuable materials benefits from robust preparative methodologies. In this work, we present a novel approach for the...
“…Rilpivirine hydrochloride (component of Complera®) was approved by FDA in 2011. Synthesis has been developed but is constantly being refined [ 109 ].…”
Section: Molecular Mechanisms Of Action Of Non-nucleoside Structured Compoundsmentioning
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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