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

Nagahisa Yamaoka, Yasuhiko Kawano, Yuko Izuhara, Toshio Miyata, Kanji Meguro

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

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 monocarboxyl derivative (10) exhibited PAI-1 inhibition comparable to the corresponding dicarboxyl compound (9f).

Original languageEnglish
Pages (from-to)615-619
Number of pages5
JournalChemical and Pharmaceutical Bulletin
Volume58
Issue number5
DOIs
Publication statusPublished - 2010 May

Keywords

  • Aminothiophenecarboxylic acid derivative
  • Inhibitor
  • Plasminogen activator inhibitor-1
  • Structure-activity relationship
  • Tissue-type plasminogen activator

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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