Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (1).

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Asano Y, Kitamura S, Ohra T, Aso K, Igata H, Tamura T, Kawamoto T, Tanaka T, Sogabe S, Matsumoto S, Yamaguchi M, Kimura H, Itoh F

Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (1).

Bioorg Med Chem. 2008 Apr 15;16(8):4715-32. doi: 10.1016/j.bmc.2008.02.027. Epub 2008 Feb 13.

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18313304 [ View in PubMed

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Abstract

A novel series of 4-phenylisoquinolones were synthesized and evaluated as c-Jun N-terminal kinase (JNK) inhibitors. Initial modification at the 2- and 3-positions of the isoquinolone ring of hit compound 4, identified from high-throughput screening, led to the lead compound 6b. The optimization was carried out using a JNK1-binding model of 6b and several compounds exhibited potent JNK inhibition. Among them, 11g significantly inhibited cardiac hypertrophy in rat pressure-overload models without affecting blood pressure and the concept of JNK inhibitors as novel therapeutic agents for heart failure was confirmed.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Pyrazolanthrone	Mitogen-activated protein kinase 8	IC 50 (nM)	110	N/A	N/A	Details