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