Synthesis of 3-amino-4-hydroxy coumarin and dihydroxy-phenyl coumarins as novel anticoagulants.
Natural and synthetic coumarin derivatives have been shown to possess several beneficial pharmacological effects. The anticoagulation and antithrombotic activities of the 4-hydroxy coumarin derivatives are well known. In this study, besides the 4-hydroxy substituent phenyl and p-methylphenyl derivatives were synthesized and confirmed on the basis of their spectral data. 3-Amino-4-hydroxy coumarin, 5,7-dihydroxy-4-phenyl coumarin and 7,8-dihydroxy-3-(4-methylphenyl)coumarin were tested in rats to determine whether they had any effect on vitamin K inhibition by investigating the prothrombin time (PT). PT values of coumarin derivatives were compared with those of warfarin (CAS 81-81-2), which is the most commonly used anticoagulant. 7,8-Dihydroxy-3-(4-methylphenyl)coumarin increased PT when compared to saline treated control group and other coumarins synthesized, 3-amino-4-hydroxy coumarin and 5,7-dihydroxy-4-phenyl coumarin.
Marmara University, Faculty of Science and Letters, Department of Chemistry, Goztepe, Istanbul, Turkey. odanis@marmara.edu.tr
Ozkan
O
Danis
Basak
B
Yuce-Dursun
Cihan
C
Gunduz
Ayse
A
Ogan
Goksel
G
Sener
Mustafa
M
Bulut
Aysen
A
Yarat
D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology*; D003374:Coumarins / Q000138:chemical synthesis* / Q000494:pharmacology*; D006490:Hemostatics / Q000037:antagonists & inhibitors; D007202:Indicators and Reagents; D008297:Male; D011517:Prothrombin Time; D051381:Rats; D017208:Rats, Wistar; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000494:pharmacology
D000925:Anticoagulants; D003374:Coumarins; D006490:Hemostatics; D007202:Indicators and Reagents; D014812:Vitamin K; D014859:Warfarin