Anagrelide hydrochloride

BeschreibungAnagrelide hydrochloride was launched in the US for thrombocytosis (essential or associated with chronic myelogenous leukemia). The imidazoquinazoline derivative can be prepared from 2,5,6-trichloro-3,4-dihydropyrimidine via alkylation with ethyl bromoacetate followed by heating with ethanolic ammonia or treatment of N-(a-amino- 5,6-dichlorobenzyl)glycine ethyl ester with cyanogen bromide. As a result of its anti-cAMP phosphodiesterase (PDE Ⅲ) activity, Anagrelide hydrochloride was initially tested as a platelet aggregation inhibitor. However it was found that at much lower concentrations it became thrombocytopenic. While the mechanism is not fully understood, it did not shorten platelet survival nor inhibit the formation of colony-forming unitsmegakaryocytes (CFU-M) but primarily interfered with the maturation of megakaryocytes (reduction in size with altered ploidy). It did decrease peripheral vascular resistance and had a positive inotropic effect.