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

• Authors: DWYER Michael; PARUCH Kamil; LABROLI Marc; ALVAREZ Carmen; KEERTIKAR Kerry; POKER Cory; ROSSMAN Randall; FISCHMANN Thierry; DUCA Jose; MADISON Vincent; PARRY David; DAVIS Nicole; SEGHEZZI Wolfgang; WISWELL Derek; GUZI Timothy
• Year of publication: 2011
• Type: Article in Periodical
• Magazine / Source: Bioorganic & Medicinal Chemistry Letters
• MU Faculty or unit: Faculty of Science
• Doi: https://doi.org/10.1016/j.bmcl.2010.10.113
• Field: Organic chemistry
• Keywords: Kinase CHK1 Pyrazolo[1 5-a]pyrimidine Template
• Description: 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.