Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: a template-based approach--part 2
| Autor: | Marc A. Labroli, Alvarez Carmen S, Randall R. Rossman, Cory Poker, Nicole Davis, Wolfgang Seghezzi, Jose S. Duca, Vincent S. Madison, David A. Parry, Derek Wiswell, Michael P. Dwyer, Timothy J. Guzi, Kamil Paruch, Thierry O. Fischmann, Kerry Keertikar |
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| Rok vydání: | 2010 |
| Předmět: |
Pyrimidine
Stereochemistry Clinical Biochemistry Regulator Drug Evaluation Preclinical Pharmaceutical Science Crystallography X-Ray Biochemistry Chemical synthesis chemistry.chemical_compound Structure-Activity Relationship Cyclin-dependent kinase Catalytic Domain Drug Discovery Structure–activity relationship CHEK1 Molecular Biology Protein Kinase Inhibitors Binding Sites biology Kinase Organic Chemistry Cyclin-Dependent Kinase 2 Pyrimidines chemistry Enzyme inhibitor Checkpoint Kinase 1 biology.protein Molecular Medicine Pyrazoles Protein Kinases |
| Zdroj: | Bioorganicmedicinal chemistry letters. 21(1) |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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