Synthesis, structure-activity relationships and stereochemical investigations of new tricyclic pyridazinone derivatives as potential STAT3 inhibitors

Daniela Masciocchi, Arianna Gelain, Federica Porta, Fiorella Meneghetti, Alessandro Pedretti, Giuseppe Celentano, Daniela Barlocco, Laura Legnani, Lucio Toma, Byoung Mog Kwon, Akira Asai, Stefania Villa

Research output: Contribution to journalArticlepeer-review

Abstract

Through a cell-based biological screening, the benzocinnolinone derivative (±)-2c was identified as a promising STAT3 inhibitor. Since SAR studies on a series of compounds structurally related to (±)-2c (1c, 2a-p, 3c, 4c, 6) showed that the latter had the most significant inhibitory activity, we investigated in depth its essential structural features. In particular, enantiomeric separation was performed, and the absolute configuration of the stereoisomers was assigned by theoretical and crystallographic studies. The biological evaluation highlighted that (S)-(-)-2c is twice as potent as (R)-(+)-2c.

Original languageEnglish
Pages (from-to)1181-1188
Number of pages8
JournalMedChemComm
Volume4
Issue number8
DOIs
Publication statusPublished - Aug 2013

ASJC Scopus subject areas

  • Biochemistry
  • Pharmaceutical Science

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