Normethyl Fentanyl Hydrochloride Salt
[CAS# 1217684-08-6]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Piperidines
• Name: Normethyl Fentanyl Hydrochloride Salt
• Synonyms: N-[(3S,4R)-3-methylpiperidin-4-yl]-N-phenylpropanamide;hydrochloride
• Molecular Formula: C₁₅H₂₃ClN₂O
• Molecular Weight: 282.81
• CAS Registry Number: 1217684-08-6
• SMILES: CCC(=O)N([C@@H]1CCNC[C@@H]1C)C2=CC=CC=C2.Cl

Discovory and Applicatios

Normethyl fentanyl hydrochloride salt is a synthetic opioid compound structurally related to fentanyl, one of the most potent μ-opioid receptor agonists used in clinical medicine. Normethyl fentanyl is characterized by the removal of the N-methyl group on the piperidine nitrogen atom of fentanyl, yielding a secondary amine in place of the tertiary amine. This subtle structural change has a significant impact on both the pharmacological and physicochemical properties of the molecule.

The synthesis of normethyl fentanyl was first described in the context of fentanyl structure-activity relationship studies aimed at understanding how various substitutions influence receptor affinity and potency. The removal of the N-methyl group generally results in a reduction in lipophilicity, which may alter the compound's pharmacokinetics, such as absorption and blood-brain barrier penetration. Nonetheless, normethyl fentanyl retains significant affinity for the μ-opioid receptor, allowing it to exhibit analgesic activity, though typically with lower potency compared to fentanyl itself.

In its hydrochloride salt form, normethyl fentanyl exists as a more stable and water-soluble variant, suitable for analytical and research purposes. The salt form allows for precise measurement and formulation, which is particularly important for controlled laboratory experiments involving in vitro binding assays or in vivo pharmacodynamic assessments. Normethyl fentanyl hydrochloride has occasionally been used in receptor binding studies to evaluate opioid receptor selectivity and to explore the effects of structural modifications on efficacy and potency.

Unlike fentanyl and many of its clinically approved analogs such as sufentanil or remifentanil, normethyl fentanyl has no accepted medical application and has not been developed or marketed as a pharmaceutical product. Its appearance in the scientific literature is limited to research studies focusing on opioid pharmacology and structure-based drug design. Because it is a known precursor or metabolite of fentanyl-related substances, it may also appear in forensic and toxicological analyses during investigations of synthetic opioid exposures.

Normethyl fentanyl is of particular interest in metabolism studies because it may form as a result of N-demethylation during the biotransformation of fentanyl in the human body. Cytochrome P450 enzymes, particularly CYP3A4, are known to catalyze N-demethylation reactions. This metabolic pathway is significant because it affects the duration of action and toxicity of fentanyl and its derivatives. Understanding normethyl fentanyl’s formation and activity assists in predicting clinical and toxicological outcomes of fentanyl use or overdose.

Due to its opioid receptor activity, normethyl fentanyl hydrochloride is classified as a controlled substance in many jurisdictions, including those that regulate fentanyl analogs as part of efforts to prevent misuse. Its structural similarity to fentanyl makes it a target for regulation under analogue provisions of controlled substances laws. Illicit synthesis and distribution of normethyl fentanyl or its derivatives could pose serious public health risks due to potential respiratory depression and overdose, especially when mixed with other opioids or used unknowingly.

In laboratory settings, normethyl fentanyl hydrochloride is handled under strict conditions due to its bioactivity and potential toxicity. It is typically used in receptor binding assays, pharmacokinetic modeling, and comparative structure-activity studies, which contribute to broader understanding of opioid mechanisms and support the development of both therapeutic opioids and opioid antagonists.

As the opioid crisis has intensified worldwide, substances like normethyl fentanyl have become focal points for both scientific investigation and regulatory enforcement. Their study contributes valuable insights into the molecular determinants of opioid activity and assists in forensic efforts to detect and control emerging synthetic opioids in the illegal drug market.