Evaluation of pyrrolin-2-one derivatives synthesized by a new practical method as inhibitors of plasminogen activator inhibitor-1 (PAI-1).
We describe in this Letter a new synthetic method for pyrrolin-2-ones as potent plasminogen activator inhibitor-1 (PAI-1) inhibitors. Pyrrolin-2-one derivatives synthesized from N-2-oxoethylamides and aldehydes in aqueous NaOH by one-pot were evaluated for their PAI-1 inhibitory activity. Among these derivatives, compounds 16 and 18 were found to possess potent PAI-1 inhibitory activity (compound 16: IC(50): 0.69microM, compound 18: IC(50): 0.65microM).
Miyazaki
Hiroshi
H
Medicinal Chemistry Laboratory, Mitsubishi Tanabe Pharma Co., Ltd, 3-16-89, Kashima, Yodogawa, Osaka 532-8505, Japan. miyazaki.hiroshi@me.mt-pharma
Miyake
Tsutomu
T
Terakawa
Yoshihiro
Y
Ohmizu
Hiroshi
H
Ogiku
Tsuyoshi
T
Ohtani
Akio
A
D000179:Acrylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry* / Q000378:metabolism; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism
D000179:Acrylates; D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D011760:Pyrrolidinones; D015842:Serine Proteinase Inhibitors