title: Evaluation of pyrrolin-2-one derivatives synthesized by a new practical method as inhibitors of plasminogen activator inhibitor-1 (PAI-1).
abstract: 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).
authors.affiliation: Medicinal Chemistry Laboratory, Mitsubishi Tanabe Pharma Co., Ltd, 3-16-89, Kashima, Yodogawa, Osaka 532-8505, Japan. miyazaki.hiroshi@me.mt-pharma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Miyake
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Terakawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohmizu
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ogiku
authors.forename: Akio
authors.initials: A
authors.lastname: Ohtani
mesh_terms: 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
chemical_list: D000179:Acrylates; D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D011760:Pyrrolidinones; D015842:Serine Proteinase Inhibitors