Phenprocoumon

Chemical Name 4-hydroxy-3-(1-phenylpropyl)-2H-1-benzopyran-2-one Common Name 3-(1-phenylpropyl)-4-hydroxycoumarin Structural Formula  

Diethyl-(1 -phenylpropyDmalonate Acetylsalicylic acid chloride Methanol 

3 parts by weight of powdered sodium in 300 parts by volume of benzene, 100 parts by weight of diethyi (l -phenylpropyl)-malonate and 72 parts by weight of acetylsalicylic acid chloride are reacted together to form diethyi 1-(o-acetoxybenzoyl)-1-(1 -phenylpropyDmalonate, which boils at 195°-198°C/0.03 mm Hg. 

3 parts of weight of diethyl 1-(o-acetoxyben2oyl)-1-(1 -phenylpropyl)-malonate are dissolved in 60 parts by volume of absolute ether and to this solution are added portion-wise at 10°C, while stirring, 2.6 parts by weight of sodium methylate. The reaction mixture is stirred for 4 hours, whereupon it is poured into ice water. The ether solution is washed neutral with ice water. After having distilled off the ether, a thick oil consisting of 3-carbethoxy-3-(1 -phenylpropyl)-4-oxo-dihydrocoumarin is obtained. This compound crystallized in butyl oxide and has a MP of 108°-109°,C. 

The 3-carbethoxy-3-(1 -phenylpropyl)-4-oxo-dihydrocoumarin may be hydrolyzed and decar-boxylated as follows. The crude product is heated to 85°C for A hour with 100 parts by volume of 5% aqueous sodium hydroxide, while agitating or stirring. To remove traces of undissolved oil, the cooled solution is treated with 1 part by weight of charcoal, whereupon it is filtrated and acidified to Congo reaction with dilute sulfuric acid. The 3-(V-phenylpropyO-4-hydroxycoumarin formed is separated off and recrystallized in 80% ethanol, whereupon it melts at 178°-179°C according to U.S. Patent 2,701,804. 

Diethyl-d -phenylpropyOmalonate Acetylsalicylic acid chloride Methanol 

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J. R. Veraait, C. Gooijer, H. Lingeman, N. H. Velthorst and U. A. Th Brinkman, Determination of phenprocoumon in plasma and urine by at-line solid-phase exti action-capillaiy electi ophoresis , 7. Pharm. Biomed. Anal. 17 1161-1166 (1998). 

Metyrapone Acetylsalicylic acid Caraspirin calcium Acetylsalicylic acid chloride Benoryiate Phenprocoumon N-Acetylsulfanilyl chloride Sulfacytine Sulfamethoxazaole 3-Acetylthiomethyl propanoic acid Captopril... 

Piperacillin sodium Diethyl-d -phenyl propyl) malonate Phenprocoumon Diethylpropyl malonate Apazone... 

The two most widely used coumarins are warfarin (US, Canada, and UK) and phenprocoumon (continental Europe). The long half-life (60 h) of prothrombin means that coumarin cannot achieve therapeutic anticoagulation for at least 5 days following initiation. Thus, for patients with acute thrombosis, oral anticoagulants are usually started only when the patient is receiving a rapidly active agent, usually UFH or LMWH. 

C)H7CI03 5538-51-2) see Benorilate Phenprocoumon (2-acetoxybenzoyl)(l-phenylpropyl)malonic acid diethyl ester... 

Mass spectrometry (MS) is also being used to add another dimension of analysis to achiral-chiral analysis. Recently, an achiral-chiral column-switching LC/LC-MS/MS method was reported for the pindolol enantiomers in human serum (Motoyama et al., 2002) and phenprocoumon metabolites (Kammerer et al., 1998). For analytes that have very poor chromophores or cannot naturally fluoresce, MS detection can be more sensitive for the underivatized form of the analyte. Also, MS detection can be particularly useful when very similar analytes that differ in mass (such as some amino acids and metabolites) cannot be satisfactorily separated chromatographically,... 

Kammerer, B., Kahlich, R., Ufer, M., Laufer, S., Gleiter, C. (2005). Achiral-chiralLC/LC-MS/ MS coupling for determination of chiral discrimination effects in phenprocoumon metabolism. Anal. Biochem. 339, 297-309. 

Phenoxybenzamine Phenprocoumon Phentolamine Phenylbutazone Phenytoin Physostigmine Phytomenadione... 

Phenprocoumon Phenprocoumon, 3-(a-ethylbenzyl)-4-hydroxycoumarin (24.1.14), is synthesized by acylating sodium salts of diethyl ester (l-phenylpropyl)butyric acid with acetylsalicylic acid chloride, which forms the compound 24.1.12, which upon reaction with sodium ethoxide cyclizes to 3-(a-ethylbenzyl)-2-carboethoxy-4-hydroxycoumarin (24.1.13). Alkaline hydrolysis of this product and further decarboxylation gives phenprocoumon (24.1.14) [21-28]. 

Phenprocoumon is used for the same indications as all of the aforementioned drugs. Synonyms of this drug are marcoumar and liquamar. 

Bishydroxycoumarin (dicoumarol) is a natural occurring anticoagulant found in sweet clover. A number of coumarin derivatives have been synthesized as anticoagulants, warfarin, phenprocoumon and acenocoumarol being most frequently used. The nonpolar carbon substituent at the 3 position required for activity is asymmetrical. The enantiomers differ in both pharmacokinetic and pharmacodynamic properties. The coumarins are marketed as racemic mixtures. 

Phenprocoumon has a long plasma half-life of 5 days and thus a duration of action that can last 7-10 days. On the other hand acenocoumarol has a half-life of 10-24 hours and therefore a shorter duration of action. The half-life of warfarin ranges from 25-60 hours and its the duration of action is 2-5 days. Both warfarin and phenprocoumon are highly protein bound and interactions may occur with other drugs that bind to albumin. 

Kruth P, Brosi E, Fux R, Morike K, Gleiter C. Ginger-associated overanticoagulation by phenprocoumon. Ann Pharmacother 2004 38 257-260. 

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