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.
Pyometra or pyometritis is a uterine infection. Though it is most commonly known as a disease of the unaltered female dog, it is also a notable human disease. It is also seen in female cattle, horses, goats, sheep, swine, cats, rabbits, hamsters, ferrets, rats and guinea pigs. Pyometra is an important disease to be aware of for any dog or cat owner because of the sudden nature of the disease and the deadly consequences if left untreated. It has been compared to acute appendicitis in humans, because both are essentially empyemas within an abdominal organ. Signs and symptoms
The most obvious symptom of open pyometra is a discharge of pus from the vulva in a female that has recently been in heat. However, symptoms of closed pyometra are less obvious. Symptoms of both types include vomiting, loss of appetite, depression, and increased drinking and urinating. Fever is seen in less than a third of female dogs with pyometra. Closed pyometra is a more serious condition than open pyometra not only because there is no outlet for the infection, but also because a diagnosis of closed pyometra can easily be missed due to its insidious nature. Bloodwork may show dehydration and/or increased white blood cell count. X-rays will show an enlarged uterus, and ultrasound will confirm the presence of a fluid filled uterus. Cause
The risk of developing pyometra differs between dog breeds. Pyometra is a result of hormonal and structural changes in the uterus lining.