Warfarin 华法林

华法林
本品是香豆素类抗凝剂的一种，在体内有对抗维生素K的作用。可以抑制维生素K参与的凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ的在肝脏的合成。对血液中已有的凝血因子 Ⅱ、Ⅶ、Ⅸ、Ⅹ并无抵抗作用。因此，不能作为体外抗凝药使用，体内抗凝也须有活性的凝血因子消耗后才能有效，起效后作用和维持时间亦较长。主要用于防治血栓栓塞性疾病。

药品名称：华法林
药物别名：苄丙酮香豆素钠，华法令钠，华福灵，华法林钠，苄丙酮香豆素
英文名称：Warfarin，Warfarin Sodium，Athrombine，COUMADIN，PA 华法林分子结构式
NAWARFIN，WARFILONE，Coumadin
分子式：C19H16O4
分子量：308.33

华法林：英文名：Warfarin ，学名为苄丙酮香豆素，是一种只可以口服的防凝血素，发明于上世纪40年代，一开始是注册为老鼠药（现名为杀鼠灵）且一上市时马上受到大众欢迎。
灭鼠灵：中文别名： 华法令；华法灵、苄丙酮香豆素；酮苄香豆素，为抗凝血型杀鼠剂，在全世界广泛使用，主要用于杀灭小家鼠，大家鼠、褐家鼠等家栖鼠，也可用于灭野鼠。杀鼠灵的作用方式是进入鼠体后表现抗凝血作用，使鼠体内出血而致死。一般投饵后三周内灭鼠率可达90%以上。

warfarin
Rodenticide
coumarin anticoagulant

NOMENCLATURE
Common name warfarin (BSI, E-ISO, BAN); warfarine ((m) F-ISO); coumafène (France); zoocoumarin (USSR); coumarins (JMAF, also applied to coumatetralyl (q.v.)); no name (The Netherlands)
IUPAC name (RS)-4-hydroxy-3-(3-oxo-1-phenylbutyl)coumarin; 3-(a-acetonylbenzyl)-4-hydroxycoumarin
Chemical Abstracts name 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one
CAS RN [81-81-2] unstated stereochemistry; [5543-58-8] (R)-(+)- isomer; [5543-57-7] (S)-(-)- isomer EEC no. 201-377-6 (for (RS)- isomers); 226-908-9 (for (R)- isomer); 226-907-3 (for (S)- isomer)

PHYSICAL CHEMISTRY
Mol. wt. 308.3 M.f. C19H16O4 Form The racemate forms colourless crystals. M.p. 161-162 ºC V.p. 1.5 ´ 10-3 mPa Solubility In water 17 mg/l (20 ºC). Very slightly soluble in benzene, diethyl ether and cyclohexane. Moderately soluble in methanol, ethanol, and isopropanol. In acetone 65, chloroform 56, dioxane 100 (all in g/l, 20 ºC). Dissolves in aqueous alkalis with the formation of water-soluble salts. Sodium salt: in water up to 400 g/l; insoluble in organic solvents. Stability Very stable, even to strong acids. pKa It is acidic

COMMERCIALISATION
History Its anticoagulant properties reported by K. P. Link et al. (J. Biol. Chem., 1944, 153, 5) at the Wisconsin Alumni Research Foundation. Patents US 2427578

APPLICATIONS
Biochemistry General internal bleeding is induced by reduction of the prothrombin content of the blood. Mode of action Anticoagulant rodenticide. Repeated ingestion is necessary to produce toxic symptoms. The (S)-(-)- isomer has 7-fold greater rodenticidal activity than the (R)-(+)- isomer (B. D. West et al., J. Am. Chem. Soc., 1961, 83,2676). Uses Control of rats and mice. There is no tendency to bait-shyness. Formulation types AB; CB; CP; GB; RB; Gel. Compatibility Compatible with other rodenticides. Selected products: 'Sakarat X' (Killgerm); mixtures: 'Cumix' (+ sulfaquinoxaline) (Kemio)

OTHER PRODUCTS
'Contrax Cuma' (Kemio); 'Musal' (Kemio); 'Sewarin' (Killgerm); 'Sewercide' (Killgerm) mixtures: 'Musal stick' (+ sulfaquinoxaline) (Kemio) Discontinued products: 'CoRax' * (Prentiss); 'RAX' * (Prentiss)

ANALYSIS
Product analysis by u.v. spectrometry (AOAC Methods, 17th Ed., 960.15; CIPAC Handbook, 1970, 1, 696) or by hplc (K. Hunter, Anal. Methods Pestic. Plant Growth Regul., 1988, 16, 154). Residues determined by hplc of a derivative (idem, ibid.).

MAMMALIAN TOXICOLOGY
Oral Acute oral LD50 for rats 186, mice 374 mg/kg. Oral LD50 for rats 1, pigs 1, cats 3, dogs 3, cattle 200 (all mg/kg daily for 5 days). Other Organ damage is observed, as well as inhibition of blood coagulation. Only slightly dangerous to humans and domestic animals when used as directed, but care must be taken with young pigs, which are especially susceptible. Toxicity class WHO (a.i.) Ib; EPA (formulation) I EC classification R61| T; R48/25| R52, R53 (for (R)-, (S)-, or (RS)- isomers)

ECOTOXICOLOGY
Birds Poultry are relatively resistant.

ENVIRONMENTAL FATE
EHC 175 (WHO, 1995) Animals Metabolites in mammals include 4-, 6-, 7-, and 8-hydroxycoumarin (R. F. Lawrence et al., Chirality, 1990, 2, 96; F. A. Sutcliffe et al., Chem. Biol. Interact., 1990, 75, 171).