Research And Synthesis Of Platelet Aggregation Inhibitor Anagrelide

The incidence of blood vessel embolic diseases is rising in recent years, and blood vessel embolic diseases are mostly constituted by coronary artery thrombus and cerebrovascular thrombus. Embolic diseases are the main cause of death and deformity, and they cause the 1/12 patients to death. In China there are 15,000,000 people died for ischemic apoplexy this decade. The critical step in normal clotting mechanism is the platelet aggregation, and the adherence, collection, releasing of platelet can cause thrombosis. Thus drugs inhibiting platelet aggregation play important roles in treating thrombus diseases and antiplatelet drugs are the hotspot for studying.Antiplatelet aggregation drugs, also named platelet function inhibitors, is sorted to 5 classes by mechanism: arachidonic acid(AA)metabolism inhibitors;drugs increasing the content of cAMP in blood platelet;NO donator drugs;acting on platelet membrane idio- antagonists and receptors drug;zymoplasm inhibitor。Anagrelide, originally characterized as an inhibitor of platelet aggregation, is an oral antiplatelet drug. The antiplatelet aggregation effects of Anagrelide have beenpartly through inhibitting of platelet phosphodiesterase activity, leading to accumulation of cAMP and elevating its levels. Its chemical name is 6,7-dichloro-l,2,3,5 -tetroimidazo[2, l-b]quinazolin-2-(3/f!)-one and its trade name is Agrylin, which has been developded by Robergts Phamaceuticals and allowed to go on sale on America in July, 1997. Anagrelide (Agrylin) has been effective in the treatment of thrombocytosis associated with myeloprolif-erative disorders. Anagrelide is the first drug as being to give approval to treat essential thrombocythemia(ET).Patent(US4146718) reported Anagrelide was synthesized from m-chloroaniline. The procedure consist of 9 steps and the yield is 8.3%. In order to reduce synthesis steps of Anagrelide , a reasonable method for industrial production was established in this paper. In this route, the initial material 1,2,3-trichlorobenzene was selected and synthesized to the final product through five steps of nitration % reduction >. cyclization. This route has the advantages of mild reaction conditions, cheaper materials, low cost and less synthesis step, etc.