Synthesis and platelet aggregation-inhibitory activities of novel 3-(2-oxopropylidene)azetidin-2-one derivatives. I.
Treatment of (E)-3-(2-hydroxypropylidene)-4-methyl-1-phenylazetidin-2-one (11) with 10% Pd/C gave (E)-(12), (Z)-3-(2-oxopropylidene)-4-methyl-1-phenylazetidin-2-one (13), 3,4-cis-(14a) and 3,4-trans-3-(2-oxopropyl)-4-methyl-1-phenylazetidin-2-one (14b). Among them, 12 and 13 were found to show potent inhibitory activities against rabbit platelet-rich plasma aggregation induced by adenosine diphosphate or collagen. Ring-expanded homologous derivatives and an acyclic analogue of 12 were also synthesized and tested for the biological activities. The azetidin-2-one skeleton bearing a 2-oxoalkylidene moiety at the 3 position was found to be essential for the platelet aggregation inhibitory activities of these compounds.
Kawashima
Y
Y
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Sato
M
M
Hatada
Y
Y
Goto
J
J
Nakashima
Y
Y
Hatayama
K
K
Shibuya
S
S
D000818:Animals; D001384:Azetidines / Q000138:chemical synthesis* / Q000494:pharmacology; D001385:Azetines / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis*; D011817:Rabbits
D001384:Azetidines; D001385:Azetines; D010975:Platelet Aggregation Inhibitors; C064174:3-(2-oxopropylidene)azetidin-2-one