Effects of chroman derivatives on platelet aggregation induced by some aggregating agents in rabbits.
1. We synthesized 10 chroman derivatives (CD-1 to CD-10) derived from khellactone, including praeruptorin A and praeruptorin B and examined the effects of these compounds on rabbit platelet aggregation. 2. These compounds exhibited an inhibitory effect on platelet-activating factor (PAF)-induced platelet aggregation and their effects were more potent on PAF-induced platelet aggregation than on adenosine triphosphate (ADP)-, arachidonate (AA)- or collagen-induced platelet aggregation. In particular, (+/-)-cis-5-methoxy-6-methoxycarbonyl-2,2-dimethyl-3,4-ditiglyloxychr oman (CD-6), (+/-)-cis-5-methoxy-6-(2-methoxycarbonylethenyl)-2,2-dimethyl- 3,4-ditiglyloxychroman (CD-8), (+/-)-cis-3,4-diacetoxy-5-methoxy-2,2-dimethyl-6-propylchroman (CD-9) and (+/-)-cis-5-methoxy-2,2-dimethyl-6-propyl-3,4-ditiglyloxychroman (CD-10) showed a moderate inhibition of PAF-induced platelet aggregation. 3. From these findings, it is suggested that compounds with potent PAF antagonist activities have the following features: (i) a tiglyloxy moiety is required at the 3 and 4 positions; and (ii) the methoxy moiety is also required at the 5 position of chroman skeleton in khellactone.
Aida
Y
Y
Hoechst Marion Roussel, Minatoku, Japan. yoko.aida@hmr.co.jp
Kasama
T
T
Fukaya
H
H
Takeuchi
N
N
Sugiyama
K
K
Tobinaga
S
S
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002839:Chromans / Q000138:chemical synthesis / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship
D002839:Chromans; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen