Synthesis, Analytical Characterization, and Human CB<sub>1</sub> Receptor Binding Studies of the Chloroindole Analogues of the Synthetic Cannabinoid MDMB-CHMICA
Sascha Münster-Müller,
Steven Hansen,
Tobias Lucas,
Arianna Giorgetti,
Lukas Mogler,
Svenja Fischmann,
Folker Westphal,
Volker Auwärter,
Michael Pütz,
Till Opatz
Affiliations
Sascha Münster-Müller
Federal Criminal Police Office, Forensic Science Institute, Äppelallee 45, 65203 Wiesbaden, Germany
Steven Hansen
Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10–14, 55128 Mainz, Germany
Tobias Lucas
Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10–14, 55128 Mainz, Germany
Arianna Giorgetti
Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy
Lukas Mogler
Institute of Forensic Medicine, Forensic Toxicology, Medical Center, University of Freiburg, Albertstr. 9, 79104 Freiburg, Germany
Svenja Fischmann
State Bureau of Criminal Investigation Schleswig-Holstein, Forensic Science Institute, Mühlenweg 166, 24116 Kiel, Germany
Folker Westphal
State Bureau of Criminal Investigation Schleswig-Holstein, Forensic Science Institute, Mühlenweg 166, 24116 Kiel, Germany
Volker Auwärter
Institute of Forensic Medicine, Forensic Toxicology, Medical Center, University of Freiburg, Albertstr. 9, 79104 Freiburg, Germany
Michael Pütz
Federal Criminal Police Office, Forensic Science Institute, Äppelallee 45, 65203 Wiesbaden, Germany
Till Opatz
Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10–14, 55128 Mainz, Germany
Synthetic cannabinoids (SCs) are one of the largest groups of new psychoactive substances (NPSs). However, the relationship between their chemical structure and the affinity to human CB1 receptors (hCB1), which mediates their psychotropic activity, is not well understood. Herein, the synthesis of the 2-, 4-, 5-, 6- and 7-chloroindole analogues of the synthetic cannabimimetic MDMB-CHMICA, along with their analytical characterization via ultraviolet–visible (UV/VIS), infrared (IR), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry, is described. Furthermore, all five derivatives of MDMB-CHMICA were analyzed for their hCB1 binding affinities. Chlorination at position 4 and 5 of the indole core reduced the binding affinity compared to MDMB-CHMICA, while the test compounds chlorinated in positions 2, 6, and 7 largely retained their binding affinities relative to the non-chlorinated parent compound.
