Synthesis of Nitrile‐Bearing Quaternary Centers by an Equilibrium‐Driven Transnitrilation and Anion‐Relay Strategy

Alazet, Sébastien; West, Michael S.; Patel, Purvish; Rousseaux, Sophie

doi:10.1002/ange.201903215

Cited by 2 publications

(1 citation statement)

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“…Nitrile group is not new in drug discovery; indeed, more than 46 nitrile‐containing drugs are prescribed for different therapeutic indications (Fleming, Yao, Ravikumar, Funk, & Shook, ), and therefore, their synthesis continues to attract much interest (Alazet, West, Patel, & Rousseaux, ). Likewise, according to the DrugBank (Wishart et al, ), there are currently 59 pharmaceuticals containing the nitrile electrophilic warhead approved for therapeutic use, while ca.…”

Section: Introductionmentioning

confidence: 99%

Molecular design aided by random forests and synthesis of potent trypanocidal agents as cruzain inhibitors for Chagas disease treatment

et al. 2020

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Cruzain is an established target for the identification of novel trypanocidal agents, but how good are in vitro/in vivo correlations? This work describes the development of a random forests model for the prediction of the bioavailability of cruzain inhibitors that are Trypanosoma cruzi killers. Some common properties that characterize druglikeness are poorly represented in many established cruzain inhibitors. This correlates with the evidence that many high-affinity cruzain inhibitors are not trypanocidal agents against T. cruzi. On the other hand, T. cruzi killers that present typical druglike characteristics are likely to show better trypanocidal action than those without such features. The random forests model was not outperformed by other machine learning methods (such as artificial neural networks and support vector machines), and it was validated with the synthesis of two new trypanocidal agents. Specifically, we report a new lead compound, Neq0565, which was tested on T. cruzi Tulahuen (β-galactosidase) with a pEC 50 of 4.9. It is inactive in the host cell line showing a selectivity index (SI = EC 50 cyto /EC 50 T. cruzi

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Section: Introductionmentioning

confidence: 99%

Molecular design aided by random forests and synthesis of potent trypanocidal agents as cruzain inhibitors for Chagas disease treatment

et al. 2020

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Trapping of Transient Organolithium Compounds

Inoue

Okano

2020

Asian J Org Chem

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Organolithium chemistry has been widely utilized in organic synthesis as a reliable tool for introducing various functional groups. The intrinsic high reactivity of organolithiums allows rapid chemical transformation; however, the transient organolithiums bearing an electrophilic moiety often cause the undesired reactions such as self-dimerization, isomerization, and decomposition, which prevent further synthetic application. In this minireview, we classify the reactions involving the short-lived organolithiums and focus on the recent progress in flow chemistry, which allows to trap the highly reactive organolithium species. In addition, this review includes other approaches using the related organometallic species that can be performed in a conventional batch reactor. To place the recent development of this field in perspective, the established strategies controlling the reactivities of the short-lived organolithiums provide a shortstep, efficient, and protective group-free synthesis of functionalized organic molecules in medicinal, agrochemical, and material chemistry.

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Synthesis of Nitrile‐Bearing Quaternary Centers by an Equilibrium‐Driven Transnitrilation and Anion‐Relay Strategy

Cited by 2 publications

References 48 publications

Molecular design aided by random forests and synthesis of potent trypanocidal agents as cruzain inhibitors for Chagas disease treatment

Molecular design aided by random forests and synthesis of potent trypanocidal agents as cruzain inhibitors for Chagas disease treatment

Trapping of Transient Organolithium Compounds

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