By Donna M. Iula, Ph.D. and Nathan K. Layle, MS - Forensic Chemistry Division, Cayman Chemical

Cinnamylpiperazines (a.k.a. acyl cinnamylpiperazines) represent a relatively new class of emerging synthetic opioids. AP-237 ("1-butyryl-4-cinnamylpiperazine" or "Buccinazine") is a therapeutic medication that was developed decades ago for pain management, and its structure represents the prototypical backbone of this class of compounds. A methylated version of AP-237 (2-methyl AP-237) began to appear on the recreational drug market in 2019. How far this class will grow in terms of new analogs is unknown, but the forensic community should be prepared. 2-methyl AP-237 has been implicated in overdose deaths, and several public alerts have been issued, but little is known about the biological activity and hazards of this class of compounds.^1-3  

This article establishes a standardized naming convention that is easy to use and can be adapted to future analogs should they appear. This naming convention takes into account modifications at all the known areas of substitution. The approach is similar to what Cayman established for the standardized naming of substituted fentanyls.⁴

Analogs of AP-237 with a substituent or substituents on the piperazine ring will be named based on which carbon the substituent is on (2, 3, 5, and/or 6). Substituents on the linker between the piperazine ring and the phenyl ring will be designated using the Greek letters α, β, and/or γ. If there is a substituent on the aryl ring portion of the N-alkyl chain, the convention will be to use the terms ortho, meta, and/or para. If the AP-237 acyl group contains an addition to the alkyl chain, substitutions will named using α^', β^', and/or γ^' to parallel the Cayman naming convention for fentanyls. 

Following this system, we have named the following analogs "2-methyl AP-237," "para-methyl AP-237," and the presumptive metabolite "γ'-hydroxy 2-methyl AP-237" to provide a precise description of where the substituents are, thereby avoiding ambiguity.⁵

When the typical AP-237 butyryl moiety is swapped for a different acyl group, the compound will be named by placing the name of the moiety that is replacing the typical AP-237 acyl group in front of the word “AP-237” (similar to how acetyl fentanyl and butyryl fentanyl are named). For example, “Propionyl AP-237” and “Valeryl AP-237” would be the preferred names for the two compounds below following this naming system.

While the origin of the name AP-237 can be traced back to a 1970s article in the Japanese Journal of Anesthesiology, the origin of AP-238 is less clear.⁶ The cinnamylpiperazine AP-238 emerged on the recreational drug market in 2020 sold under this name. Using this new proposed naming convention, an alternative name for AP-238 that makes its structure more evident would be “2,6-dimethyl Propionyl AP-237”. 

As with any naming system, there will be exceptions to the rule, especially since the future direction of an emerging chemical class is unknown. Cayman will keep abreast of new analogs that may appear in forensic casework or on the grey market and respond quickly to provide a reference standard. If you are having trouble identifying or finding a compound of interest, please contact our technical support department. Cayman can also provide assistance in the identification of unknown compounds and provides other tools on our Forensic Science Products page such as our Spectral Library, GC-MS Search Tool, and Wall Poster Guides to help chemists identify and name novel analogs.

View all cinnamylpiperazines reference standards

To cite this naming system: Iula, D.M. and Layle, N. Standardized Naming System for the Emerging Cinnamylpiperazine Class of Synthetic Opioids. Article, Cayman Chemical (2021).

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References

1. Vandeputte, M.M., Cannaert, A., and Stove, C.P. In vitro functional characterization of a panel of non-fentanyl opioid new psychoactive substances. Arch. Toxicol. 94(11), 3819-3830 (2020).

2. Alert Regarding 2-Methyl AP-237– June 11, 2021. In: deadiversion.usdoj.gov [Internet]. Available from: https://www.deadiversion.usdoj.gov/dea_tox/announcements/2-Methyl_AP-237.pdf

3. 2-Methyl AP-237. In: npsdiscovery.org [Internet]. Available from: https://www.npsdiscovery.org/wp-content/uploads/2019/06/2-Methyl-AP-237_072219_NMSLabs_Report-1.pdf

4. Iula, D.M. Standardized Naming of Substituted Fentanyls. Article, Cayman Chemical (2018).

5. Hassanien, S.H., Layle, N.K., Holt, M.C., et al. 2-methyl AP-237. Cayman NPS Metabolism Monograph Issue 1 (2019).

6. Nishimura, N., Kiuchi, M., Kanetake, Y., et al. Clinical evaluation of a new analgesic agent Ap-237. Masui 19(6), 653-656 (1970).