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DOI: 10.1055/s-0031-1296335
Synthesis of 3-amino-4-hydroxy coumarin and dihydroxy-phenyl coumarins as novel anticoagulants
Publication History
Publication Date:
03 December 2011 (online)
Abstract
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.
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Literature
- 1 Murray RDH, Mendez J, Brown SA. The Natural Coumarins-Occurrence, Chemistry And Biochemistry. Chichester: John Whiley; 1982
- 2 Yuce B, Danis O, Ogan A, Sener G, Bulut M, Yarat A. Antioxidative and lipid lowering effects of 7, 8-dihydroxy-3-(4-methylphenyl) coumarin in hyperlipidemic rats. Arzneimittelforschung. 2009; 59 (3) 129-34
- 3 Kostova I. Synthetic and natural coumarins as cytotoxic agents. Curr Med Chem Anticancer Agents. 2005; 5 (1) 29-46
- 4 Spino C, Dodier M, Sotheeswaran S. Anti-HIV coumarins from calophyllum seed oil. Bioorg Med Chem. 1998; 8: 3475-8
- 5 Kontogiorgis C, Hadjipavlou-Litina D. Synthesis and antiinflammatory activity of coumarin derivatives. J Med Chem. 2005; 48 (20) 6400-8
- 6 Ren P, Stark PY, Johnson RL, Bell RG. Warfarin and the metabolism of vitamin K1 . Biochem Pharmacol. 1974; 23: 3355-7
- 7 O’Reillly RA. Vitamin K and the oral anticoagulant drugs. Annu Rev Med. 1976; 27: 245-61
- 8 Beillerot A, Dominguez J, Kirsch G, Bagrel D. Synthesis and protective effects of coumarin derivatives against oxidative stress induced by doxorubicin. Bioorg Med Chem. 2008; 18: 1102-5
- 9 O’Kennedy R, Thones RD. Coumarins: biology, applications and mode of actions. Chichester: John Whiley; 1997: 304
- 10 Gammon WD, Hunter R, Wilson S. An effcient synthesis of 7-hydroxy-2, 6-dimethylchromeno[3,4-d] oxazol-4-one a protected fragment of novenamine. Tetrahedron. 2005; 10: 683-8
- 11 Buu-Hoi NP, Saint-Ruf G, Lobert B. Oxygen heterocycles. Part XIV. Hydroxylated 3-aryl- and 3-pyridyl-coumarins. J Chem Soc C. 1969; 2069-70
- 12 Raad I, Terreux R, Richomme P, Matera E, Dumontet C, Raynaud J et al. Structure-activity relationship of natural and synthetic coumarins inhibiting the multidrug transporter P-glycoprotein. Bioorg Med Chem. 2006; 14: 6979-87
- 13 D’Andrea G, D’Ambrosia R, Margaglione M. Oral anticoagulants: pharmacogenetics relationship between genetic and non-genetic factors. Blood Rev. 2008; 22: 127-40
- 14 Hirsch J, Dalen J, Deykin D, Poller L. Oral anticoagulants. Chest. 1992; 102: 312S-326S
- 15 Gage B, Milligan P. Pharmacology and pharmacogenetics of warfarin and other coumarins when used with supplements. Thromb Res. 2005; 117: 55-9
- 16 Hirsh J, Fuster V. Guide to anticoagulant therapy. Part 2: Oral anticoagulants. Circulation. 1995; 91 (2) 1469-80
- 17 Manolov I, Danchev ND. Synthesis, toxicological and pharmacological assessment of some 4-hydroxycoumarin derivatives. Eur J Med Chem. 1995; 30: 531-5
- 18 Bruno O, Brullo C, Schenone S, Bondavalli F, Ranise A, Tognolini M. Synthesis, antiplatelet and antithrombotic activities of new 2-substitued benzopyrano[4,3-d]pyrimidin-4-cycloamines and 4-amino/cycloamino-benzopyrano [4,3-d]pyrimidin-5-ones. Bioorg Med Chem. 2006; 14: 121-30
- 19 Arora RB, Mathur CN. Relationship between structure and anticoagulant activity of coumarin derivatives. Br J Pharmacol Chemother. 1963; 20: 29-35