MEDICINAL CHEMISTRY

Warfarin and other coumarin derivatives are antagonists of vitamin K. Thus they act by
depressing the vitamin K-dependent synthesis of coagulation factors 11 (prothrombin),
VII, IX and X, and of the anticoagulant protein C and its protein cofactor protein S.
Official Drugs
Warfarin Sodium, B.P., I.P.: Warfarin sodium is the sodium salt of (RS)-4-hydroxy-3-
(3-oxo-l-phenylbutyl)-coumarin. It is a white powder and hygroscopic. It is very soluble
in water. It should be kept in an airtight container and protected from light. Warfarin
sodium is readily absorbed from the gastrointestinal tract. It can also be absorbed through
the skin. It is extensively bound to plasma proteins and its plasma half-life is about 37
hours. Warfarin is transformed into inactive metabolites by the liver and kidneys. They
are excreted in urine and stool. Warfarin is used in the prevention and treatment of deepvein
thrombosis or pulmonary embolism. It is equally effective either orally or
intravenously. Warfarin should not be given to patients who are haemorrhaging,
Warfarin is used as a racemic mixture, and however the S-isomer is reported to be more
potent. Usual dose of warfarin sodium is 10 mg daily by mouth for 2 days, but may be
lower for patients with particular risk of haemorrhage. Subsequent maintenance doses
usually range from 3 to 9 mg daily.
Preparation: Warfarin Tablets, B.P. Proprietary Names: COUMADIN; PANWARFIN
Warfarin Sodium tablets, I.P
Warfarin Sodium Clathrate, B.P., I.P.: Warfarin sodium Clathrate is the Clathrate of
the sodium salt of (RS)-4-hydroxy-3-(3-oxo-l-phenylbutyl)-coumarin with propan-2-ol. It
consists of warfarin sodium and propan-2-ol in the molecular proportion of 2:1. It
contains approximately 92% of warfarin sodium. It is a white powder and is very soluble
in water. It should be kept in an airtight container and protected from light. It has actions
and uses similar to those of warfarin sodium. Preparation: Warfarin Tablets, B.P.
Acenocoumarin/Nicoumalone, B.P, I.P.: Nicoumalone is (RS)-4-hydroxy-3-[1-(4nitrophenyl)-3-oxobutyl]
coumarin. It is a white to brownish white powder, practically
insoluble in water. It is stored in light-resistant containers. Nicoumalone is readily
absorbed when given by mouth. It is excreted chiefly in the urine mainly as metabolites.
It is extensively bound to plasma proteins. Nicoumalone has actions and uses similar to
those of warfarin sodium. It is administered orally. Though used as a racemic mixture,
the R(+)-enantiomer of nicoumalone is reported to be pharmacologically active
component of nicoumalone. The initial dose of nicoumalone is 12 to 20 mg; subsequent
doses are given in accordance with the needs of the patient.
Preparation: Nicoumalone Tablets, B.P., I.P. Proprietary Name: SINTHROME
C. Indanedione
Indanedione derivatives, such as phenindione and anisidione, were conceived as ring
contracted analogues of coumarins. Like coumarins they also act as oral anticoagulants
by inhibiting the synthesis of prothrombin and other factors VII, IX and X.