Benoxaprofen

Benoxaprofen, also known as Benoxaphen, is a chemical compound with the formula C16H12ClNO3. It is a nonsteroidal anti-inflammatory drug (NSAID) and was marketed under the brand name Oraflex in the United States and as Opren in Europe by Eli Lilly and Company. Lilly suspended sales of Oraflex in 1982 after reports from the British government and the U.S. Food and Drug Administration (FDA) of adverse effects and deaths linked to the drug. Benoxaprofen, also known as Benoxaphen, is a chemical compound with the formula C16H12ClNO3. It is a nonsteroidal anti-inflammatory drug (NSAID) and was marketed under the brand name Oraflex in the United States and as Opren in Europe by Eli Lilly and Company. Lilly suspended sales of Oraflex in 1982 after reports from the British government and the U.S. Food and Drug Administration (FDA) of adverse effects and deaths linked to the drug. Benoxaprofen was discovered by a team of Lilly chemists at its British laboratory. This laboratory was assigned to explore new anti-arthritic compounds in 1966. Lilly applied for patents on benoxaprofen seven years later and also filed for permission from the FDA to start testing the drug on humans. It had to undergo the three-step clinical testing procedure required by the Federal Government. Lilly began Phase I of the progress by testing a handful of healthy human volunteers. These tests had to prove that the drug posed no clear and immediate safety hazards. In Phase II a larger number of human subjects, including some with minor illnesses, was tested. The drug’s effectiveness and safety was the major target of these tests. Phase III was the largest test and began in 1976. More than 2,000 arthritis patients were administered the drug by more than 100 physicians. The physicians reported the results to the Lilly Company. When the company formally requested to begin marketing the drug in January 1980 with the FDA, the document consisted of more than 100,000 pages of test results and patients’ records.Benoxaprofen was first marketed abroad: in 1980 the drug was released for marketing in the UK. It came on the market in May 1982 in the USA. When benoxaprofen was on the market as Oraflex in the USA the first sign of trouble came for the Lilly Company. The British Medical Journal reported in May 1982 that physicians in the UK believed that the drug was responsible for at least 12 deaths, mainly caused by kidney and liver failure. A petition was filed to have Oraflex removed from the market. On the fourth of August 1982 the British government temporarily suspended sales of the drug in UK ‘on grounds of safety’. The British Committee on the Safety of Medicines declared, in a telegram to the FDA, that it had received reports of more than 3,500 adverse side-effects among patients who had used Oraflex. There were also 61 deaths, most of which were of elderly people. Almost simultaneously, the FDA said it had reports of 11 deaths in the USA among Oraflex users, most of which were caused by kidney and liver damage. The Eli Lilly Company suspended sales of benoxaprofen that afternoon. The molecular formula of benoxaprofen is C16H12ClNO3 and the systematic (IUPAC) name is 2-propionic acid. The molecule has a molecular mass of 301.050568 g/mol. Benoxaprofen is essentially a planar molecule. This is due to the co-planarity of the benzoxazole and phenyl rings, but the molecule also has a non-planar side chain consisting of the propanoic acid moiety which acts as a carrier group. These findings were obtained from X-ray crystallographic measurements made at the Lilly Research Centre.