Improved synthesis, resolution, absolute configuration determination and biological evaluation of HLM006474 enantiomers

[Display omitted] An improved green synthesis of the E2F inhibitor HLM0066474 is described, using solvent-free and microwave irradiation conditions. The two enantiomers are separated using semi-preparative separation on Chiralpak ID and their absolute configuration is determined by vibrational circu...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2019-02, Vol.29 (3), p.380-382
Hauptverfasser:	Rosales-Hurtado, Miyanou, Lebeau, Alexandre, Bourouh, Cyril, Cebrian-Torrejon, Gerardo, Albalat, Muriel, Jean, Marion, Naubron, Jean-Valère, Annicotte, Jean-Sébastien, Benfodda, Zohra, Meffre, Patrick
Format:	Artikel
Sprache:	eng
Schlagworte:	Absolute configuration determination Aminopyridines - chemistry Aminopyridines - pharmacology Betti reaction Biochemistry Biochemistry, Molecular Biology Biological activity Chemical engineering Chemical Sciences Circular Dichroism Dose-Response Relationship, Drug E2F1 Transcription Factor - antagonists & inhibitors E2F1 Transcription Factor - metabolism HEK293 Cells HLM006474 enantiomers Humans Hydroxyquinolines - chemistry Hydroxyquinolines - pharmacology Life Sciences Microwave assisted synthesis Molecular biology Molecular Structure Organic chemistry Solvent-free reaction Stereoisomerism Structure-Activity Relationship
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Zusammenfassung:	[Display omitted] An improved green synthesis of the E2F inhibitor HLM0066474 is described, using solvent-free and microwave irradiation conditions. The two enantiomers are separated using semi-preparative separation on Chiralpak ID and their absolute configuration is determined by vibrational circular dichroism (VCD) analysis. Biological evaluation of both enantiomers on E2F1 transcriptional activity reveals that the (+)-R, but not the (−)-S enantiomer is biologically active in repressing E2F1 transcriptional activity.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2018.12.037