کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1361565 981466 2008 18 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (1)
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (1)
چکیده انگلیسی

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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 8, 15 April 2008, Pages 4715–4732
نویسندگان
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