Structure-based design, synthesis and SAR of a novel series of thiopheneamidine urokinase plasminogen activator inhibitors.
The serine protease urokinase plasminogen activator (uPA) is thought to play a central role in tumor metastasis and angiogenesis. Molecular modeling studies suggest that 5-thiomethylthiopheneamidine inhibits uPA by binding at the S1 pocket of the active site. Further structure based elaboration of this residue resulted in a novel class of potent and selective inhibitors of uPA.
Subasinghe
N L
NL
3-Dimensional Pharmaceuticals Inc., 665 Stockton Drive, Exton, PA 19341, USA. nalin@3dp.com
Illig
C
C
Hoffman
J
J
Rudolph
M J
MJ
Wilson
K J
KJ
Soll
R
R
Randle
T
T
Green
D
D
Lewandowski
F
F
Zhang
M
M
Bone
R
R
Spurlino
J
J
DesJarlais
R
R
Deckman
I
I
Molloy
C J
CJ
Manthey
C
C
Zhou
Z
Z
Sharp
C
C
Maguire
D
D
Crysler
C
C
Grasberger
B
B
D000963:Antimetabolites / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D006801:Humans; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000502:physiology
D000963:Antimetabolites; D013876:Thiophenes; D014568:Urokinase-Type Plasminogen Activator