Design, synthesis, and evaluation of orally active inhibitors of plasminogen activator inhibitor-1 (PAI-1) production.
A novel series of butadiene-imide 1 (T-686) derivatives having an inhibitory activity against PAI-1 production was synthesized and evaluated their biological activities and DMPK profiles, in which 15k (T-2639) was selected as the best compound based on its strong antithrombotic activity and good bioavailability.
Miyazaki
Hiroshi
H
Medicinal Chemistry Laboratory, Mitsubishi Tanabe Pharma Co., Ltd, 3-16-89, Kashima, Yodogawa, Osaka 532-8505, Japan.
Ogiku
Tsuyoshi
T
Sai
Hiroshi
H
Ohmizu
Hiroshi
H
Murakami
Jun
J
Ohtani
Akio
A
D000284:Administration, Oral; D000818:Animals; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004285:Dogs; D004333:Drug Administration Routes; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008956:Models, Chemical; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D012995:Solubility; D013388:Succinimides / Q000138:chemical synthesis / Q000494:pharmacology
D001597:Benzylidene Compounds; D017395:Plasminogen Activator Inhibitor 1; D013388:Succinimides; C104988:T 686