Structure-activity relationships of new 2-acylamino-3-thiophenecarboxylic acid dimers as plasminogen activator inhibitor-1 inhibitors.

Abstract

Small molecule inhibitors of plasminogen activator inhibitor (PAI)-1 have been reported to date but their clinical effects still remain unknown. The present study was undertaken to investigate the structure-activity relationships (SAR) of newly synthesized 2-acylamino-3-thiophenecarboxylic acid dimers based upon a core structure of TM5001 (1) and TM5007 (2) that we have previously identified as orally effective PAI-1 inhibitors. In general, compounds possessing bulky or/and hydrophobic substituents (e.g. phenyl, isobutyl group) on the both thiophene rings showed potent PAI-1 inhibitory activities irrespective of the positions of the substitution. The mono-carboxyl derivative (10) exhibited PAI-1 inhibition comparable to the corresponding dicarboxyl compound (9f).

Cite this paper

@article{Yamaoka2010StructureactivityRO, title={Structure-activity relationships of new 2-acylamino-3-thiophenecarboxylic acid dimers as plasminogen activator inhibitor-1 inhibitors.}, author={Nagahisa Yamaoka and Yasuhiko Kawano and Yuko Izuhara and Toshio Miyata and Kanji Meguro}, journal={Chemical & pharmaceutical bulletin}, year={2010}, volume={58 5}, pages={615-9} }