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 journalArticle

9 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

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Acidity
Hydroxyl Radical
Phosphotransferases
5-hydroxyindole

All Science Journal Classification (ASJC) codes

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

Cite this

Synthesis and structure based optimization of 2-(4-phenoxybenzoyl)-5- hydroxyindole as a novel CaMKII inhibitor. / Komiya, Masafumi; Asano, Shigehiro; Koike, Nobuyuki; Koga, Erina; Igarashi, Junetsu; Nakatani, Shogo; Isobe, Yoshiaki.

In: Bioorganic and Medicinal Chemistry, Vol. 20, No. 23, 01.12.2012, p. 6840-6847.

Research output: Contribution to journalArticle

Komiya, Masafumi ; Asano, Shigehiro ; Koike, Nobuyuki ; Koga, Erina ; Igarashi, Junetsu ; Nakatani, Shogo ; Isobe, Yoshiaki. / Synthesis and structure based optimization of 2-(4-phenoxybenzoyl)-5- hydroxyindole as a novel CaMKII inhibitor. In: Bioorganic and Medicinal Chemistry. 2012 ; Vol. 20, No. 23. pp. 6840-6847.
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