Design, synthesis and structure activity relationship of potent pan-PIM kinase inhibitors derived from the pyridyl carboxamide scaffold

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• 作者：Gisele A. Nishiguchi^a ; ^{gisele.nishiguchi@novartis.com" class="auth_mail" title="E-mail the corresponding author} ; Matthew T. Burger^a ; Wooseok Han^a ; Jiong Lan^a ; Gordana Atallah^a ; Victoriano Tamez^a ; Mika Lindvall^a ; Cornelia Bellamacina^a ; Pablo Garcia^b ; Paul Feucht^b ; Tatiana Zavorotinskaya^b ; Yumin Dai^b ; Kent Wong^a
• 关键词：Pim kinase ; pan-PIM kinase inhibitor ; Hematological malignancies
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 May 2016
• 年：2016
• 卷：26
• 期：9
• 页码：2328-2332
• 全文大小：2131 K

文摘

The Pim proteins (1, 2 and 3) are serine/threonine kinases that have been found to be upregulated in many hematological malignancies and solid tumors. As a result of overlapping functions among the three isoforms, inhibition of all three Pim kinases has become an attractive strategy for cancer therapy. Herein we describe our efforts in identifying potent pan-PIM inhibitors that are derived from our previously reported pyridyl carboxamide scaffold as part of a medicinal chemistry strategy to address metabolic stability.