Synthesis and structure based optimization of 2-(4-phenoxybenzoyl)-5- hydroxyindole as a novel CaMKII inhibitor

Masafumi Komiya, Shigehiro Asano, Nobuyuki Koike, Erina Koga, Junetsu Igarashi, Shogo Nakatani, Yoshiaki Isobe

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Based on 2-(4-phenoxybenzoyl)-5-hydroxyindole (2), a novel structural class of CaMKII inhibitors were synthesized and further optimized. The strong acidity of the hydroxyl group and the lipophilic group at the 4 and 6-positions were found to be necessary for strong CaMKII inhibition. Compound 25 was identified as a promising compound with 50-fold more potent inhibitory activity for CaMKII than 2. Compound 25 also showed high selectivity for CaMKII over off-target kinases.

Original languageEnglish
Pages (from-to)6840-6847
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number23
DOIs
Publication statusPublished - Dec 1 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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