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
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
677-681Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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