Ohmefentanyl is an extremely potent opioid analgesic drug which selectively binds to the µ-opioid receptor. Ohmefentanyl is one of the most potent μ-opioid receptor agonists known, comparable to super-potent opioids such as carfentanil and etorphine which are only legally used for tranquilizing large animals such as elephants in veterinary medicine. In mouse studies, the most active isomer 3R,4S,βS-ohmefentanyl was 28 times more powerful as a painkiller than fentanyl, the chemical from which it is derived, and 6300 times more powerful than morphine. Ohmefentanyl has three stereogenic centers and eight stereoisomers, which are named F9201–F9208. Researchers are studying the different pharmaceutical properties of these isomers. The 4″-fluoro analogue of the 3R,4S,βS isomer of ohmefentanyl is one of the most potent opioid agonists yet discovered, possessing an analgesic potency approximately 18,000 times that of morphine. Other analogues with potency higher than that of ohmefentanyl itself include the 2′-fluoro derivative, and derivatives where the N-propionyl group was replaced by N-methoxyacetyl or 2-furamide groups, or a carboethoxy group is added to the 4-position of the piperidine ring. The latter is listed as being up to 30,000 times more potent than morphine. Side effects of fentanyl analogues are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Illicitly used fentanyl analogues have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.
Synthesis
The synthesis of ohmefentanyl is more complex than the synthesis of fentanyl and some of its related analogues, requiring more reagents, equipment, and time compared to the synthesis of fentanyl. The synthesis of ohmefentanyl is accomplished starting from 1-Benzyl-3-methyl-4-piperidinone from which the imine is formed by reaction with aniline. The obtained imine is reduced using sodium borohydride to yield the amine which is then reacted with propionic anhydride. In the next step of the synthesis, the benzyl protecting group is removed from the piperidine ring by catalytic hydrogenation to give the secondary amine which is then reacted with 2-bromoacetophenone, after which the ketone is reduced with sodium borohydride to form ohmefentanyl.
