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

  • Bioorg Med Chem Lett. 2011 Jan 1;21(1):471-4. doi: 10.1016/j.bmcl.2010.10.114.
Marc Labroli  1 ,  Kamil Paruch ,  Michael P Dwyer ,  Carmen Alvarez ,  Kartik Keertikar ,  Cory Poker ,  Randall Rossman ,  Jose S Duca ,  Thierry O Fischmann ,  Vincent Madison ,  David Parry ,  Nicole Davis ,  Wolfgang Seghezzi ,  Derek Wiswell ,  Timothy J Guzi
Affiliations
  • 1. Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States. [email protected]
PMID: 21094607 DOI: 10.1016/j.bmcl.2010.10.114
Abstract

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.