Synthesis and evaluation of coumarin alpha-methylene-gamma-butyrolactones: a new class of platelet aggregation inhibitors.
In a search for new inhibitors of platelet aggregation, certain coumarin-bearing alpha-methylene-gamma-butyrolactones were synthesized and evaluated for inhibitory activity against thrombin (Thr)-, arachidonic acid (AA)-, collagen (Col)-, and platelet-activating factor (PAF)-induced aggregation in washed rabbit platelets. These compounds were efficiently synthesized from commercially available 7-hydroxycoumarin or its derivatives. Among them, 7-[(2,3,4,5-tetrahydro-4-methylene-5-oxo-2-phenyl-2-furanyl) methoxy]-2H-1-benzopyran-2-one (3d) showed the most potent inhibition of AA- and PAF- induced aggregation, with IC50 values of 3.65 and 16.36 microM respectively.
Chen
Y L
YL
School of Chemistry, Kaohsiung Medical College, Taiwan, Republic of China.
Wang
T C
TC
Liang
S C
SC
Teng
C M
CM
Tzeng
C C
CC
D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D003374:Coumarins / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D013329:Structure-Activity Relationship
D003374:Coumarins; D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D000255:Adenosine Triphosphate