Study On Synthetic Process Of Ambrisentan

Pulmonary arterial hypertension (PAH) is characterized by vascular obstructionand the variable presence of vasoconstriction, leading to increased pulmonaryvascular resistance and right-sided heart failure.Therapies approved for PAH targetinclude three main pathways-Phosphodiesterase, prostacyclin and endothelinreceptor antagonists.Ambrisentan is the first oral treatment of PAH, its pharmacological mechanismfor PAH is reducing membrane hypertrophy in pulmonary in order to expand thepore size of blood vessels; blocking the ET receptor of vascular smooth muscle tolower the tension of the pulmonary vascular.For the preparation of ambrisentan, benzophenone was used as the startingmaterial. It went through a series of reactions, such as Darzens condensation,methanolysis and hydrolysis to give2-hydroxy-3-methoxy-3,3-diphenylpropionicacid. The latter was subjected to resolution to give(S)-2-hydroxy-3-methoxy-3,3-diphenylpropionic acid. Finally, it reacted with4,6-dimethyl-2-methylsulfonyl pyrimidine via a nucleophilic substitution to giveambrisentan. The overall yield of the title compound was30%from benzophenone.