Structure and activity relationship of 2-(substituted benzoyl)-hydroxyindoles as novel CaMKII inhibitors

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

doi:10.1016/j.bmcl.2011.01.012

Structure and activity relationship of 2-(substituted benzoyl)-hydroxyindoles as novel CaMKII inhibitors

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1456-8. doi: 10.1016/j.bmcl.2011.01.012. Epub 2011 Jan 8.

Authors

Masafumi Komiya¹, Shigehiro Asano, Nobuyuki Koike, Erina Koga, Junetsu Igarashi, Shogo Nakatani, Yoshiaki Isobe

Affiliation

¹ Chemistry Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd, Konohana-ku, Osaka, Japan. [email protected]

PMID: 21292482
DOI: 10.1016/j.bmcl.2011.01.012

Abstract

A series of novel 2-substituted-5-hydroxyindoles were synthesized and evaluated for their inhibitory activity against CaMKII. Structure and activity relationship results indicated that potent inhibitory activity could be achieved by modification at the para-position of the phenyl ring of the high throughput screening hit compound 2. Among the prepared compounds, we identified 14 as a novel CaMKII inhibitor with an activity stronger than that of KN-93, a known CaMKII inhibitor.

MeSH terms

Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors*
Enzyme Activation / drug effects
Indoles / chemical synthesis
Indoles / chemistry*
Indoles / pharmacology*
Inhibitory Concentration 50
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology*
Structure-Activity Relationship

Substances

Indoles
Protein Kinase Inhibitors
Calcium-Calmodulin-Dependent Protein Kinase Type 2