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: Patrick-Denis St-Cœur, Dean Ferguson, Pier Morin Jr, Mohamed Touaibia
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 346 Issue 2 Pg. 91-7 (Feb 2013) ISSN: 1521-4184 [Electronic] Germany
• PMID: 23300119 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• 6-(3-(piperazin-1-yl)propanoyl)benzo(d)oxazol-2(3H)-one
• Antineoplastic Agents
• Benzoxazoles
• Phosphodiesterase Inhibitors
• Piperazines
• Phosphoric Diester Hydrolases
• alkylglycerophosphoethanolamine phosphodiesterase

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Benzoxazoles (chemical synthesis, chemistry, pharmacology)
• Brain Neoplasms (enzymology, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Design
• Glioblastoma (enzymology, pathology)
• Humans
• Molecular Structure
• Phosphodiesterase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Phosphoric Diester Hydrolases (metabolism)
• Piperazines (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship