Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel antiproliferative agents: exploration of core and headpiece structure-activity relationships.
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.
Powell
Dennis
D
Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA. powelld@wyeth.com
Gopalsamy
Ariamala
A
Wang
Yanong D
YD
Zhang
Nan
N
Miranda
Miriam
M
McGinnis
John P
JP
Rabindran
Sridhar K
SK
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D015689:Oncogene Protein p21(ras) / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors
D000577:Amides; D007202:Indicators and Reagents; D011743:Pyrimidines; D016159:Tumor Suppressor Protein p53; D015689:Oncogene Protein p21(ras)