title: Pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides as novel anti-proliferative agents: parallel synthesis for lead optimization of amide region.
abstract: A novel series of p21 chemoselective agents containing a pyrazolo[1,5-a]pyrimidin-7-yl phenyl amides were identified by high throughput screening. Optimization of the amide region by parallel synthesis and the iterative design toward understanding structure-activity relationship to improve potency are described. The isopropyl carbamate derivative 34 was identified as a highly chemoselective agent displaying a potency of 51 nM in the p21 deficient cell line.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA. gopalsa@wyeth.com
authors.forename: Ariamala
authors.initials: A
authors.lastname: Gopalsamy
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: John W
authors.initials: JW
authors.lastname: Ellingboe
authors.forename: Hwei-Ru
authors.initials: HR
authors.lastname: Tsou
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Erick
authors.initials: E
authors.lastname: Honores
authors.forename: Dennis
authors.initials: D
authors.lastname: Powell
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*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011720:Pyrazoles; D011743:Pyrimidines