Structure-based design, synthesis and SAR of a novel series of thiopheneamidine urokinase plasminogen activator inhibitors

Authors
Subasinghe, NL Illig, C Hoffman, J Rudolph, MJ Wilson, KJ Soll, R Randle, T Green, D Lewandowski, F Zhang, M Bone, R Spurlino, J DesJarlais, R Deckman, I Molloy, CJ Manthey, C Zhou, Z Sharp, C Maguire, D Crysler, C Grasberger, B
Citation
Nl. Subasinghe et al., Structure-based design, synthesis and SAR of a novel series of thiopheneamidine urokinase plasminogen activator inhibitors, BIOORG MED, 11(11), 2001, pp. 1379-1382
Citations number
21
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
11
Year of publication
2001
Pages
1379 - 1382
Database
ISI
SICI code
0960-894X(20010604)11:11<1379:SDSASO>2.0.ZU;2-I
Abstract
The serine protease urokinase plasminogen activator (uPA) is thought to pla y a central role in tumor metastasis and angiogenesis. Molecular modeling s tudies suggest that 5-thiomethylthiopheneamidine inhibits uPA by binding at the S1 pocket of the active site. Further structure based elaboration of t his residue resulted in a novel class of potent and selective inhibitors of uPA. (C) 2001 Elsevier Science Ltd. All rights reserved.