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

doi:10.1016/j.bmc.2012.09.048

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 journal › Article › peer-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 language	English
Pages (from-to)	6840-6847
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	23
DOIs	https://doi.org/10.1016/j.bmc.2012.09.048
Publication status	Published - Dec 1 2012
Externally published	Yes

All Science Journal Classification (ASJC) codes

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

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10.1016/j.bmc.2012.09.048

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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.",

author = "Masafumi Komiya and Shigehiro Asano and Nobuyuki Koike and Erina Koga and Junetsu Igarashi and Shogo Nakatani and Yoshiaki Isobe",

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AU - Komiya, Masafumi

AU - Asano, Shigehiro

AU - Koike, Nobuyuki

AU - Koga, Erina

AU - Igarashi, Junetsu

AU - Nakatani, Shogo

AU - Isobe, Yoshiaki

PY - 2012/12/1

Y1 - 2012/12/1

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AB - 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.

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

Abstract

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