Indanedione derivatives-General method of preparation

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Chapter: Medicinal Chemistry : Coagulants

i. Phenindione ii. Thrombolytics (Fibrinolytics) a. Streptokinase b. Urokinase c. Anistrepalse d. Aspirin


Indanedione derivatives—General method of preparation

Synthesis of Phenindione, Anisindione, and Bromindione

These 1,3-indandiones have been recognized for their anticoagulant activity.

i. Phenindione

Properties and uses: Phenindione exists as white crystalline powder, very slightly soluble in water, slightly soluble in ethanol and ether. Used as oral anticoagulant.

Assay: To the sample, add ethanol and warm it, cool to room temperature, add 10% v/v solution of bromine in ethanol, and allow standing with occasional shaking. Add 2-naphthol and shake until the colour of the bromine is discharged. Add water, and dilute potassium iodide solution and titrate the liberated iodine against 0.1 M sodium thiosulphate using starch mucilage as indicator.

Dosage forms: Phenindione tablets I.P., B.P.


ii. Thrombolytics (Fibrinolytics)

Fibrinolytics are drugs used to lyse thrombi and to recanalize occluded blood vessels mainly coronary artery. Anticoagulants are designed to prevent thrombus formation. A proteolytic enzyme, known as plasmin, which is released by its precursor protein plasminogen causes the destruction or dissolution of a thrombus. Plasminogen activators (e.g. streptokinase, urokinase) bring about this conversion (Fig. 1.2).

Certain other compounds have been found to promote the synthesis of various plasminogen activators. For example, anabolic steroids, act indirectly as fibrinolytic agents. All these agents are useful in the treatment of pulmonary embolic and acute coronary thrombosis. Streptokinase and urokinase are commonly used fibrinolytic agents in the treatment of acute thromboembolic diseases.


a. Streptokinase

Streptokinase is obtained from group-C beta haemolytic Streptococci. It is inactive; therefore, to be active it must be converted to plasminogen, which causes proteolysis of plasmin. It is typically used in myocardial infarctions and arterial thrombosis.


b. Urokinase

It is isolated from the human urine, now prepared from the cultures of human renal cells. It is nonantigenic and is a glycosylate serine protease containing 41 amino acid residues. It is a substrate for plasminogen, which is activated to plasmin.


c. Anistrepalse

It is a streptokinase–plasminogen complex in which plasminogen is isolated and acts as a slow released form of plasminogen activator. Coupling of the streptokinase–plasminogen complex to p-amidinophenylp-anisate blocks the catalytic centre of the complex, but allows it to bind to fibrin. As the anisoyl group is slowly hydrolyzed in vivo, the complex is allowed to bind to fibrin prior to activation. It is used in the management of acute myocardial infarction.


d. Aspirin

Synthesis and drug profile is discussed in sec I, NSAIDs.

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