title: Development of chemical probes: toward the mode of action of a methylene-linked di(aryl acetate) E1.
abstract: Analogues of the novel inhibitor of the PI3-K/PKB pathway, 2-[5-(2-chloroethyl)-2-acetoxy-benzyl]-4-(2-chloroethyl)-phenyl acetate (E1), have been prepared and preliminary SAR performed. This established that at least one of the chloroethyl para-substituents could be removed or modified and the ability to inhibit PKB/Akt activation retained. Synthetic methodologies were then developed to methylene-linked aryl acetates for use as molecular probes to identify the target of compound E1.
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London, WC1H OAJ, UK.
authors.forename: Mark E B
authors.initials: ME
authors.lastname: Smith
authors.forename: Richard M
authors.initials: RM
authors.lastname: Gunn
authors.forename: Evelyn
authors.initials: E
authors.lastname: Rosivatz
authors.forename: Lok H
authors.initials: LH
authors.lastname: Mak
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Woscholski
authors.forename: Helen C
authors.initials: HC
authors.lastname: Hailes
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010648:Phenylacetates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010648:Phenylacetates; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt