Design and Synthesis of 4,5-disubstituted-thiophene-2-amidines as potent urokinase inhibitors

M. Jonathan Rudolph, Carl R. Illig, Nalin L. Subasinghe, Kenneth J. Wilson, James B. Hoffman, Troy Randle, David Green, Chris J. Molloy, Richard M. Soll, Frank Lewandowski, Marie Zhang, Roger Bone, John C. Spurlino, Ingrid C. Deckman, Carl Manthey, Celia Sharp, Diane Maguire, Bruce L. Grasberger, Renée L. DesJarlais, Zhao Zhou

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32 Scopus citations


A study of the S1 binding of lead 5-methylthiothiophene amidine 3, an inhibitor of urokinase-type plasminogen activator, was undertaken by the introduction of a variety of substituents at the thiophene 5-position. The 5-alkyl substituted and unsubstituted thiophenes were prepared using organolithium chemistry. Heteroatom substituents were introduced at the 5-position using a novel displacement reaction of 5-methylsulfonylthiophenes and the corresponding oxygen or sulfur anions. Small alkyl group substitution at the 5-position provided inhibitors equipotent with 3 but possessing improved solubility.

Original languageEnglish (US)
Pages (from-to)491-495
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number3
StatePublished - Feb 11 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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