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This is followed by condensations with chloroacetyl chloride and methylamine to complete the diketopiperazine ring: Subsequently, the FDA approved vardenafil in 2003, and tadalafil in 2003. Tadalafil was approved in 2009 in the United States for the treatment of pulmonary arterial hypertension and is under regulatory review in other regions for this condition. In 1994, Pfizer scientists discovered that sildenafil, which also inhibits the PDE5 enzyme, caused penile erection in men participating in a clinical study of a heart medicine.
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