title: Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel antiproliferative agents: exploration of core and headpiece structure-activity relationships.
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.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA. powelld@wyeth.com
authors.forename: Dennis
authors.initials: D
authors.lastname: Powell
authors.forename: Ariamala
authors.initials: A
authors.lastname: Gopalsamy
authors.forename: Yanong D
authors.initials: YD
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Miriam
authors.initials: M
authors.lastname: Miranda
authors.forename: John P
authors.initials: JP
authors.lastname: McGinnis
authors.forename: Sridhar K
authors.initials: SK
authors.lastname: Rabindran
mesh_terms: 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
chemical_list: D000577:Amides; D007202:Indicators and Reagents; D011743:Pyrimidines; D016159:Tumor Suppressor Protein p53; D015689:Oncogene Protein p21(ras)