The environmental concerns of the synthesis of aprepitant became so great that Merck research team decided to withdraw the drug from clinical trials and attempt to create a different synthesis of aprepitant.The gamble of taking the drug out of clinical trials proved to be successful when shortly afterwards the team of Merck researchers came up with an alternative and more environmentally friendly synthesis of aprepitant. The new process works by four compounds of similar size and complexity being fused together. This therefore is a much simpler process and requires only three steps, half the number of the original synthesis. The new process begins by enantiopure trifluoromethylated phenyl ethanol being joined to a racemic morpholine precursor. This results in the wanted isomer crystallizing on the top of the solution and the unwanted isomer remaining in the solution. The unwanted isomer is then converted to the wanted one by the chemist controlling the reaction conditions and a process known as crystallization-induced asymmetric transformation occurring. By the end of this step a secondary amine, the base of the drug, is formed. The second step involves the fluorophenyl group being attached to the morpholine ring. Once this has been achieved the third and final step can initiated. This step involved a side chain of triazolinone being added to the ring. Once this step has been successfully completed a stable molecule of aprepitant has been produced.This more streamlined route yields around 76% more aprepitant than the original process and reduces the operating cost by a significant amount.
Aprepitant, sold under the brand name Emend among others, is a medication used to prevent chemotherapy-induced nausea and vomiting (CINV) and to prevent postoperative nausea and vomiting (PONV). It may be used together with ondansetron and dexamethasone. It is taken by mouth or administered by intravenous injection.Common side effects include tiredness, loss of appetite, diarrhea, abdominal pain, hiccups, itchiness, pneumonia, and blood pressure changes. Other severe side effects may include anaphylaxis. While use in pregnancy does not appear to be harmful, such use has not been well studied. Aprepitant belongs to the class of neurokinin-1 receptor antagonists medications. It works by blocking substance P from attaching to the NK1 receptors.Aprepitant was approved for medical use in the European Union and the United States in 2003. It is made by Merck & Co. It is on the World Health Organizations List of Essential Medicines. Medical uses
Aprepitant is used to prevent chemotherapy-induced nausea and vomiting (CINV) and to prevent postoperative nausea and vomiting (PONV). It may be used together with ondansetron and dexamethasone. Mechanism of action
Aprepitant is classified as an NK1 antagonist because it blocks signals given off by NK1 receptors. This, therefore, decreases the likelihood of vomiting in patients. NK1 is a G protein-coupled receptor located in the central and peripheral nervous system. This receptor has a dominant ligand known as Substance P (SP). SP is a neuropeptide, composed of 11 amino acids, which sends impulses and messages from the brain.