Title: Warfarin
CAS Registry Number: 81-81-2
CAS Name: 4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one
Additional Names: 3-(a-acetonylbenzyl)-4-hydroxycoumarin; 1-(4¢-hydroxy-3¢-coumarinyl)-1-phenyl-3-butanone; 3-a-phenyl-b-acetylethyl-4-hydroxycoumarin; WARF compound 42
Trademarks: Rodex (Hacco); Sakarat X (Killgerm); Warfotox (Aimco)
Molecular Formula: C19H16O4
Molecular Weight: 308.33
Percent Composition: C 74.01%, H 5.23%, O 20.76%
Literature References: Coumarin anticoagulant. Marketed as the racemate; the S(-)-form is the more potent isomer. Prepn: M. A. Stahmann et al., US 2427578 (1947 to Wisconsin Alumni Res. Found.). Resolution and abs configuration: B. D. West et al., J. Am. Chem. Soc. 83, 2676 (1961). Effect on vitamin K metabolism: R. G. Bell et al., Biochemistry 11, 1959 (1972). Conformation in soln: E. J. Valente et al., J. Med. Chem. 20, 1489 (1977). Toxicity studies: E. C. Hagan, J. L. Radomski, J. Am. Pharm. Assoc. Sci. Ed. 42, 379 (1953); N. Back et al., Pharmacol. Res. Commun. 10, 445 (1978). Comprehensive description: S. A. Babhair et al., Anal. Profiles Drug Subs. 14, 423-452 (1985). Stereospecific HPLC determn in plasma: P. R. Ring, J. M. Bostick, J. Pharm. Biomed. Anal. 22, 573 (2000). Review of rodenticide mechanisms of action and resistance: H. H. W. Thijssen, Pestic. Sci. 43, 73-78 (1995). Review of pharmacology and therapeutic efficacy: J. Hirsh et al., Chest 102, Suppl., 312S-326S (1992); of pharmacokinetics and effect of genetic variants: H. Takahashi, H. Echizen, Clin. Pharmacokinet. 40, 587-603 (2001). Clinical comparison with aspirin following myocardial infarction: M. Hurlen et al., N. Engl. J. Med. 347, 969 (2002).
Properties: Crystals from alc, mp 161°. uv max (water, pH 10): 308 nm (e 13610). Soluble in acetone, dioxane. Moderately sol in methanol, ethanol, isopropanol, some oils. Freely sol in alkaline aq solns (forms a water-soluble sodium salt). Practically insol in water, benzene, cyclohexane, Skellysolves A and B. Warfarin has an acidic enol which forms metallic salts and an acetate, mp 117-118°, and a ketone which forms an oxime, mp 182-183° and a 2,4-dinitrophenylhydrazone, mp 215-216°.
Melting point: mp 161°; mp 117-118°; mp 182-183°; mp 215-216°
Absorption maximum: uv max (water, pH 10): 308 nm (e 13610)
Derivative Type: Sodium salt
CAS Registry Number: 129-06-6
Trademarks: Coumadin (BMS); Marevan (Goldshield); Warfilone (Merck & Co.)
Molecular Formula: C19H15NaO4
Molecular Weight: 330.31
Percent Composition: C 69.09%, H 4.58%, Na 6.96%, O 19.38%
Properties: Slightly bitter, crystalline powder. Discolored by light. Very sol in water; freely sol in alcohol; very slightly sol in chloroform, ether. LD50 in male rats, female rats, mice, rabbits (mg/kg): 323, 58, 374, ~800 orally (Hagen); also reported as LD50 in male, female rats (mg/kg): 100.3, 8.7 orally (Back).
Toxicity data: LD50 in male rats, female rats, mice, rabbits (mg/kg): 323, 58, 374, ~800 orally (Hagen); also reported as LD50 in male, female rats (mg/kg): 100.3, 8.7 orally (Back)
CAUTION: Potential symptoms of overexposure to warfarin are hematuria, back pain; hematoma of arms and legs; epistaxis, bleeding lips and mucous membrane hemorrhage; abdominal pain, vomiting and fecal blood; petechial rash; abnormal hematologic indices. See NIOSH Pocket Guide to Chemical Hazards (DHHS/NIOSH 97-140, 1997) p 334. See also Clinical Toxicology of Commercial Products, R. E. Gosselin et al., Eds. (Williams & Wilkins, Baltimore, 5th ed., 1984) Section III, pp 395-397.
Use: Rodenticide.
Therap-Cat: Anticoagulant.
Keywords: Anticoagulant. |