title: PF-8380 and closely related analogs: synthesis and structure-activity relationship towards autotaxin inhibition and glioma cell viability.
abstract: A series of PF-8380 analogs, a recently developed autotaxin inhibitor, was explored. Inhibition of autotaxin by these analogs, as well as by all PF-8380 synthetic intermediates, shows the importance of meta-dichlorobenzyl and benzo[d]oxazol-2(3H)-one fragments. However, analogs 8 and 9, bearing only the benzo[d]oxazol-2(3H)-one moiety, are more cytotoxic on the LN229 glioblastoma cell line than PF-8380 and temozolomide (TMZ).
authors.affiliation: Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada.
authors.forename: Patrick-Denis
authors.initials: PD
authors.lastname: St-Cœur
authors.forename: Dean
authors.initials: D
authors.lastname: Ferguson
authors.forename: Pier
authors.initials: P
authors.lastname: Morin
authors.forename: Mohamed
authors.initials: M
authors.lastname: Touaibia
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D005909:Glioblastoma / Q000201:enzymology / Q000473:pathology; D006801:Humans; D015394:Molecular Structure; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000099189:Lysophospholipase D
chemical_list: D000970:Antineoplastic Agents; D001583:Benzoxazoles; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D010879:Piperazines; D000099189:Lysophospholipase D; C550725:6-(3-(piperazin-1-yl)propanoyl)benzo(d)oxazol-2(3H)-one