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

研究成果: ジャーナルへの寄稿 › 学術誌 › 査読

12 被引用数 (Scopus)

抄録

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.

本文言語	英語
ページ（範囲）	6840-6847
ページ数	8
ジャーナル	Bioorganic and Medicinal Chemistry
巻	20
号	23
DOI	https://doi.org/10.1016/j.bmc.2012.09.048
出版ステータス	出版済み - 12月 1 2012
外部発表	はい

!!!All Science Journal Classification (ASJC) codes

生化学
分子医療
分子生物学
薬科学
創薬
臨床生化学
有機化学

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10.1016/j.bmc.2012.09.048

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title = "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.",

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

year = "2012",

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doi = "10.1016/j.bmc.2012.09.048",

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journal = "Bioorganic and Medicinal Chemistry",

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T1 - Synthesis and structure based optimization of 2-(4-phenoxybenzoyl)-5- hydroxyindole as a novel CaMKII inhibitor

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

N2 - 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.

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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SN - 0968-0896

VL - 20

SP - 6840

EP - 6847

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

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ER -

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

抄録

!!!All Science Journal Classification (ASJC) codes

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