Exploiting Chemical Toolboxes for the Expedited Generation of Tetracyclic Quinolines as a Novel Class of PXR Agonists.


Journal

ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073

Informations de publication

Date de publication:
11 Apr 2019
Historique:
received: 03 10 2018
accepted: 27 12 2018
entrez: 19 4 2019
pubmed: 19 4 2019
medline: 19 4 2019
Statut: epublish

Résumé

The discovery of lead compounds relies on the iterative generation of structure-activity relationship data resulting from the synthesis and biological evaluation of hit analogues. Using traditional approaches, a significant time delay may occur from compound design to results, leading to slow and expensive hit-to-lead explorations. Herein, we have exploited the use of chemical toolboxes to expedite lead discovery and optimization. In particular, the integration of flow synthesizers, automation, process analytical technologies, and computational chemistry has provided a prototype system enabling the multicomponent flow synthesis, in-line analysis, and characterization of chiral tetracyclic quinolines as a novel class of PXR agonists. Within 29 compounds, a novel template

Identifiants

pubmed: 30996817
doi: 10.1021/acsmedchemlett.8b00459
pmc: PMC6466813
doi:

Types de publication

Journal Article

Langues

eng

Pagination

677-681

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

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Auteurs

Bruno Cerra (B)

Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, I-06123 Perugia, Italy.

Andrea Carotti (A)

Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, I-06123 Perugia, Italy.

Daniela Passeri (D)

TES Pharma, Via Corso Vannucci 47, I-06121 Perugia, Italy.

Roccaldo Sardella (R)

Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, I-06123 Perugia, Italy.

Giada Moroni (G)

Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, I-06123 Perugia, Italy.

Alessandro Di Michele (A)

Department of Department of Physics and Geology, University of Perugia, Via A. Pascoli, I-06123 Perugia, Italy.

Antonio Macchiarulo (A)

Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, I-06123 Perugia, Italy.

Roberto Pellicciari (R)

TES Pharma, Via Corso Vannucci 47, I-06121 Perugia, Italy.

Antimo Gioiello (A)

Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, I-06123 Perugia, Italy.

Classifications MeSH