Ohmefentanyl
[CAS# 78995-14-9]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Piperidines
• Name: Ohmefentanyl
• Synonyms: beta-Hydroxy-3-methylfentanyl; N-[1-(2-hydroxy-2-phenylethyl)-3-methylpiperidin-4-yl]-N-phenylpropanamide
• Molecular Formula: C₂₃H₃₀N₂O₂
• Molecular Weight: 366.50
• CAS Registry Number: 78995-14-9
• SMILES: CCC(=O)N(C1CCN(CC1C)CC(C2=CC=CC=C2)O)C3=CC=CC=C3

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 516.6±50.0 ºC 760 mmHg (Calc.)^*
• Flash point: 266.2±30.1 ºC (Calc.)^*
• Index of refraction: 1.586 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Controlled Substance: DEA Drug Code Number: 9831

Discovory and Applicatios

Ohmefentanyl is a highly potent synthetic opioid analgesic structurally related to fentanyl, first synthesized in China during the 1970s as part of a series of compounds designed to enhance analgesic potency while maintaining or improving safety profiles. It belongs to the 4-anilidopiperidine class and features several structural modifications that significantly increase its affinity for the μ-opioid receptor.

The compound is a derivative of fentanyl wherein a hydroxyl group and a methyl group are introduced at specific positions on the piperidine ring, producing a stereochemically complex structure with multiple chiral centers. The presence of these chiral centers results in several stereoisomers of ohmefentanyl, each possessing differing levels of potency. Among these, the 3R,4S,βS-isomer is notably the most potent, reported to be hundreds to thousands of times more powerful than morphine, depending on the animal model used. This extreme potency has made ohmefentanyl one of the most potent opioid agonists ever studied.

Despite its exceptional potency, ohmefentanyl has not been adopted for clinical use due to its high risk of respiratory depression and the difficulties in controlling dosing accurately at such low effective concentrations. Instead, its primary applications have remained within the field of pharmacological research, where it has been used to explore opioid receptor interactions and to assess the effects of stereochemistry on opioid activity. It has provided valuable insight into the relationship between chemical structure and pharmacological activity in opioid ligands.

The synthesis of ohmefentanyl involves constructing the phenethylpiperidine core typical of fentanyl analogs, followed by the introduction of chiral substituents at the 3- and 4-positions of the piperidine ring. Stereoselective synthesis or chiral resolution is required to isolate specific isomers. The stereochemical complexity of ohmefentanyl adds to the difficulty of its illicit manufacture, though it also contributes to the scientific understanding of how stereochemistry influences receptor binding and efficacy.

Illicit use of ohmefentanyl or its analogs has been rare compared to simpler fentanyl derivatives, but its potential for misuse exists due to its extraordinary potency. A small miscalculation in dosage can lead to rapid fatal overdose. Consequently, ohmefentanyl is classified as a controlled substance in many countries, including under Schedule I in the United States, indicating no accepted medical use and a high potential for abuse.

Due to the threat posed by such potent opioids, forensic and analytical chemistry efforts have focused on developing sensitive methods for detecting ohmefentanyl in biological samples and seized materials. Techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) are employed to identify and quantify trace amounts, especially given the compound’s activity at microgram or nanogram levels. Reference standards and stereoisomer-specific assays are often required for accurate detection.

The emergence of compounds like ohmefentanyl has underscored the need for international cooperation in monitoring novel synthetic opioids. While ohmefentanyl itself has not seen widespread use, it has inspired the design of additional analogs with similarly high potency. The constant evolution of such substances presents a significant challenge to public health and regulatory frameworks, emphasizing the necessity of real-time surveillance, chemical analysis, and legislative adaptability to address the risks posed by ultra-potent synthetic opioids.

References

1991. [3H]ohmefentanyl preferentially binds to mu-opioid receptors but also labels sigma-sites in rat brain sections. European Journal of Pharmacology, 193(2).
DOI: 10.1016/0014-2999(91)90149-k

1996. Molecular modeling of mu opioid receptor and its interaction with ohmefentanyl. Zhongguo Yao Li Xue Bao, 17(2).
PMID: 9772668

2003. Ohmefentanyl stereoisomers induce changes of CREB phosphorylation in hippocampus of mice in conditioned place preference paradigm. Cell Research, 13(1).
DOI: 10.1038/sj.cr.7290148