title: Synthesis and biological evaluation of 2-anilino-4-substituted-7H-pyrrolopyrimidines as PDK1 inhibitors.
abstract: PDK1, a biological target that has attracted a large amount of attention recently, is responsible for the positive regulation of the PI3K/Akt pathway that is often activated in a large number of human cancers. A series of second-generation 2-anilino-4-substituted-7H-pyrrolopyrimidines were synthesised by installation of various functions at the 4-position of the 7H-pyrrolopyrimidine scaffold. All compounds were screened against the isolated PDK1 enzyme and dose response analysis was obtained on the best compounds of the series.
authors.affiliation: Department of Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Vic 3086, Australia.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: O'Brien
authors.affiliation: Department of Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Vic 3086, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Brzozowski
authors.affiliation: Department of Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Vic 3086, Australia.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Buskes
authors.affiliation: Department of Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Vic 3086, Australia.
authors.forename: Leslie W
authors.initials: LW
authors.lastname: Deady
authors.affiliation: Department of Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Vic 3086, Australia. Electronic address: b.abbott@latrobe.edu.au.
authors.forename: Belinda M
authors.initials: BM
authors.lastname: Abbott
mesh_terms: D006801:Humans; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D013329:Structure-Activity Relationship
chemical_list: C000631429:PDK1 protein, human; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; C527741:pyrrolopyrimidine; D017346:Protein Serine-Threonine Kinases
keywords: 2-Anilino-4-substituted-pyrrolopyrimidines; 3-Phosphoinositide-dependent kinase 1 (PDK1); Buchwald–Hartwig cross-coupling; Inhibitor; Suzuki cross-coupling