Synthesis and evaluation of pyrrolin-2-one compounds, a series of plasminogen activator inhibitor-1 inhibitors.
A novel series of furan-2-one and pyrrolin-2-one derivatives having PAI-1 (plasminogen activator inhibitor-1) inhibitory activity were synthesized and evaluated for their antithrombotic activity in a rat arterial thrombosis model. Among the synthesized compounds, 5f (T-1776Na) was found to have good selectivity for PAI-1 over other enzymes and high antithrombotic activity.
Miyazaki
Hiroshi
H
Medicinal Chemistry Laboratory, Mitsubishi Tanabe Pharma Co., Ltd, Japan. miyazaki.hiroshi@me.mt-pharma.co.jp
Ogiku
Tsuyoshi
T
Sai
Hiroshi
H
Moritani
Yasunori
Y
Ohtani
Akio
A
Ohmizu
Hiroshi
H
D000818:Animals; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry* / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
C545000:(3-(5-oxo-3,4-diphenyl-1,5-dihydropyrrol-(2Z)-ylidenemethyl)phenoxy)acetic acid sodium salt; D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D011758:Pyrroles; D011759:Pyrrolidines