Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: A template-based approach—Part 2

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• 作者：Marc Labroli ; Kamil Paruch ; Michael P. Dwyer ; Carmen Alvarez ; Kartik Keertikar ; Cory Poker ; R ; all Rossman ; Jose S. Duca ; Thierry O. Fischmann ; Vincent Madison ; David Parry ; Nicole Davis ; Wolfgang Segh
• 关键词：Kinase ; CHK1 ; Pyrazolo[1 ; 5-a]pyrimidine ; CDK ; Cell cycle ; Inhibitors
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：1 January 2011
• 年：2011
• 卷：21
• 期：1
• 页码：471-474
• 全文大小：1494 K

文摘

Previous efforts by our group have established pyrazolo[1,5-a]pyrimidine as a viable core for the development of potent and selective CDK inhibitors. As part of an effort to utilize the pyrazolo[1,5-a]pyrimidine core as a template for the design and synthesis of potent and selective kinase inhibitors, we focused on a key regulator in the cell cycle progression, CHK1. Continued SAR development of the pyrazolo[1,5-a]pyrimidine core at the C5 and C6 positions, in conjunction with previously disclosed SAR at the C3 and C7 positions, led to the discovery of potent and selective CHK1 inhibitors.