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

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.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Komiya M,Asano S,Koike N,Koga E,Igarashi J,Nakatani S,Isobe Y

doi

10.1016/j.bmc.2012.09.048

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

6840-7

issue

23

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(12)00769-9

journal_volume

20

pub_type

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