Synthesis of novel benzo-fused heteroaryl derivatives as Ca 2+/calmodulin-dependent protein kinase II inhibitors

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Based on the structure activity relationship of 2-(4-phenoxybenzoyl)-5- hydroxyindole (1), a novel structural class of Ca2+ /calmodulin-dependent protein kinase II (CaMKII) inhibitors were synthesized. We show in this study that the acidic proton at the N(1)-position of the indole moiety is not essential for CaMKII inhibitory activity. Among the synthesized compounds, we found the benzofuran and benzothiazole derivative as promising scaffolds for the developement of potent CaMKII inhibitors. In particular, compounds 8 and 14 inhibited CaMKII with IC50 values of 24 nM and 32 nM, respectively.

Original languageEnglish
Pages (from-to)1094-1097
Number of pages4
JournalChemical and Pharmaceutical Bulletin
Volume61
Issue number10
DOIs
Publication statusPublished - Oct 1 2013
Externally publishedYes

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Protein Kinase Inhibitors
Derivatives
Structure-Activity Relationship
Scaffolds
Inhibitory Concentration 50
Protons

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Drug Discovery

Cite this

Synthesis of novel benzo-fused heteroaryl derivatives as Ca 2+/calmodulin-dependent protein kinase II inhibitors. / Komiya, Masafumi; Asano, Shigehiro; Koike, Nobuyuki; Koga, Erina; Igarashi, Junetsu; Nakatani, Shogo; Isobe, Yoshiaki.

In: Chemical and Pharmaceutical Bulletin, Vol. 61, No. 10, 01.10.2013, p. 1094-1097.

Research output: Contribution to journalArticle

Komiya, Masafumi ; Asano, Shigehiro ; Koike, Nobuyuki ; Koga, Erina ; Igarashi, Junetsu ; Nakatani, Shogo ; Isobe, Yoshiaki. / Synthesis of novel benzo-fused heteroaryl derivatives as Ca 2+/calmodulin-dependent protein kinase II inhibitors. In: Chemical and Pharmaceutical Bulletin. 2013 ; Vol. 61, No. 10. pp. 1094-1097.
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