Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel antiproliferative agents: exploration of core and headpiece structure-activity relationships

Dennis Powell; Ariamala Gopalsamy; Yanong D Wang; Nan Zhang; Miriam Miranda; John P McGinnis; Sridhar K Rabindran

doi:10.1016/j.bmcl.2006.12.116

Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel antiproliferative agents: exploration of core and headpiece structure-activity relationships

Bioorg Med Chem Lett. 2007 Mar 15;17(6):1641-5. doi: 10.1016/j.bmcl.2006.12.116. Epub 2007 Jan 13.

Authors

Dennis Powell¹, Ariamala Gopalsamy, Yanong D Wang, Nan Zhang, Miriam Miranda, John P McGinnis, Sridhar K Rabindran

Affiliation

¹ Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA. [email protected]

PMID: 17275298
DOI: 10.1016/j.bmcl.2006.12.116

Abstract

A novel series of antiproliferative agents containing pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides, selective for p21-deficient cells, were identified by high-throughput screening. Exploration of the SAR relationships in the headpiece, core, and tailpiece is described. Strict steric, positional, and electronic requirements were observed, with a clear preference for both core nitrogens, a thienoyl headpiece, and meta substituted tailpiece.

MeSH terms

Amides / chemical synthesis*
Amides / pharmacology*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects*
Colonic Neoplasms / drug therapy
Colonic Neoplasms / pathology
Computer Simulation
Drug Evaluation, Preclinical
Humans
Indicators and Reagents
Models, Molecular
Molecular Conformation
Oncogene Protein p21(ras) / antagonists & inhibitors
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology*
Structure-Activity Relationship
Tumor Suppressor Protein p53 / antagonists & inhibitors

Substances

Amides
Indicators and Reagents
Pyrimidines
Tumor Suppressor Protein p53
Oncogene Protein p21(ras)