Review of the Patent Literature: Synthesis and Final Forms of Antiviral Drugs Tecovirimat and Baloxavir Marboxil

  title={Review of the Patent Literature: Synthesis and Final Forms of Antiviral Drugs Tecovirimat and Baloxavir Marboxil},
  author={David Lewis Hughes},
  journal={Organic Process Research \& Development},
  • D. Hughes
  • Published 21 June 2019
  • Chemistry
  • Organic Process Research & Development
This article reviews synthetic routes and final polymorphic forms of two recently approved antiviral drugs, TPOXX (tecovirimat) for the treatment of smallpox and Xofluza (baloxavir marboxil), a treatment for influenza. The patent literature was the source of information for synthetic routes and final forms. 

Antiinfectives for Systemic Use, 3. Antivirals

  • A. Kleemann
  • Biology, Chemistry
    Ullmann's Encyclopedia of Industrial Chemistry
  • 2022
The article contains sections titled: J05AB Nucleosides and Nucleotides excluding RTIs; NNRTIs, and J05AR Antivirals for Treatment of HIV Infections, Combinations.

Synthetic Approaches to the New Drugs Approved During 2018.

This annual review describes the most likely process-scale synthetic approaches to thirty-nine new chemical entities approved for the first time globally in 2018.

Development of a Quality Controllable and Scalable Process for the Preparation of 7,8-Difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-ol: A Key Intermediate for Baloxavir Marboxil

A novel six-step synthesis of 7,8-difluoro-6,11-dihydrodibenzo[b,e]thiepin-11-ol (1) is described. Starting with 3,4-difloro-2-methylbenzoic acid and using diphenyl disulfide as an ideal sulfur sou...

Recent advances in the synthesis of bridgehead (or ring-junction) nitrogen heterocycles via transition metal-catalyzed C–H bond activation and functionalization

An update on recent advances in the synthesis of bridgehead nitrogen fused heterocycles via transition metal-catalyzed C–H activation and functionalization is reported.

Photorelease of a metal-binding pharmacophore from a Ru(II) polypyridine complex.

The presented inhibitor-Ru(ii) polypyridine conjugate is an example of computationally-guided drug design for light-activated drug release and may help reveal new avenues for the prodrugging of metalloenzyme inhibitors.

Syntheses and crystal structures of the anhydride 4-oxatetracyclo[,6.08,10]dodec-11-ene-3,5-dione and the related imide 4-(4-bromophenyl)-4-azatetracyclo[,6.08,10]dodec-11-ene-3,5-dione

The Diels–Alder cycloaddition of cycloheptatriene and maleic anhydride produces the title carboxylic anhydride; reaction of this anhydride with 4-bromophenylaniline forms the corresponding

Baloxavir Marboxil: An Original New Drug against Influenza

The drug is now in post-marketing pharmacovigilance phase, and its interest will be especially re-evaluated in the future during the annual flu outbreaks.



Review of Synthetic Routes and Final Forms of Integrase Inhibitors Dolutegravir, Cabotegravir, and Bictegravir

  • D. Hughes
  • Chemistry
    Organic Process Research & Development
  • 2019
A third inhibitor, cabotegravir, is in Phase 3 development, and a continuation of a series of series of approvals for integrase inhibitors for the treatment of HIV.

An efficient and highly diastereoselective synthesis of GSK1265744, a potent HIV integrase inhibitor.

A novel synthesis of GSK1265744, a potent HIV integrase inhibitor, is described. The synthesis is highlighted by an efficient construction of the densely functionalized pyridinone core as well as a

Tricyclononene carboxamide derivatives as novel anti-HIV-1 agents.

Oral Tecovirimat for the Treatment of Smallpox

Findings suggested that the nonhuman primate was the more conservative model for the estimation of the required drug exposure in humans, and tecovirimat is being advanced as a therapy for smallpox in accordance with the FDA Animal Rule.

The new drugs of 2018

  • L. Jarvis
  • Political Science
    C&EN Global Enterprise
  • 2019
Pharmaceutical industry productivity was robust in 2018, a year in which the US Food and Drug Administration approved a record 59 new drugs. The new high-water mark for innovation comes as companies

Photocatalytic decarboxylative reduction of carboxylic acids and its application in asymmetric synthesis.

The application of this method to the synthesis of enantioenriched 1-aryl-2, 2,2,2-trifluoroethyl chiral amines starting from natural α-amino acids further testifies to the utility of the developed photocatalytic decarboxylative reduction protocol.

N-(3,3a,4,4a,5,5a,6,6a-Octahydro-1,3-dioxo-4,6- ethenocycloprop[f]isoindol-2-(1H)-yl)carboxamides: Identification of novel orthopoxvirus egress inhibitors.

Using structure--activity relationship information inferred from early hits, compound 14 was identified as a potent, orally bioavailable first-in-class inhibitor of orthopoxvirus egress from infected cells and has entered Phase I clinical trials.

Verläuft die thermische Cycloaddition von Maleinsäureanhydrid an Cycloheptatrien, 7H‐Benzocyclohepten und 7H‐Benzocyclohepten‐7,7‐dicarbonitril nach [4π + 2π] oder [2π + 2π + 2π]?

In der thermischen Umsetzung von 7H-Benzocyclohepten (5) mit Maleinsaureanhydrid (2) entstehen neben Produkten (15–17 u.a.), die auf En-Reaktion und/oder Hydridabstraktion zuruckgehen, zu 6 bzw. 1%

Crystallization-induced diastereomer transformations.