Synthesis and in Vitro Cannabinoid Receptor 1 Activity of Recently Detected Synthetic Cannabinoids 4F-MDMB-BICA, 5F-MPP-PICA, MMB-4en-PICA, CUMYL-CBMICA, ADB-BINACA, APP-BINACA, 4F-MDMB-BINACA, MDMB-4en-PINACA, A-CHMINACA, 5F-AB-P7AICA, 5F-MDMB-P7AICA, and 5F-AP7AICA.

@article{Cannaert2020SynthesisAI,
  title={Synthesis and in Vitro Cannabinoid Receptor 1 Activity of Recently Detected Synthetic Cannabinoids 4F-MDMB-BICA, 5F-MPP-PICA, MMB-4en-PICA, CUMYL-CBMICA, ADB-BINACA, APP-BINACA, 4F-MDMB-BINACA, MDMB-4en-PINACA, A-CHMINACA, 5F-AB-P7AICA, 5F-MDMB-P7AICA, and 5F-AP7AICA.},
  author={Annelies Cannaert and Eric Sparkes and Edward Pike and Jia Lin Luo and Ada Fang and Richard C. Kevin and Ross Ellison and Roy R. Gerona and Samuel D. Banister and Christophe P. Stove},
  journal={ACS chemical neuroscience},
  year={2020}
}
Synthetic cannabinoid receptor agonists (SCRAs) are an evolving class of new psychoactive substances (NPS) with structurally diverse compounds emerging each year. Due to the rapid pace at which these drugs enter the market, there is often little or nil information regarding the pharmacology of these substances despite widespread human use. In this study, 12 recently emerged SCRAs (reported between 2018 and 2020) were synthesized, analytically characterized, and pharmacologically evaluated using… 
Structure-activity relationships for 5F-MDMB-PICA and its 5F-pentylindole analogs to induce cannabinoid-like effects in mice
TLDR
It is demonstrated that 5F-MDMB-PICA is a potent SCRA, and subtle alterations to head group composition can have profound influence on pharmacological effects at CB1.
Putative Synthetic Cannabinoids MEPIRAPIM, 5F-BEPIRAPIM (NNL-2), and Their Analogues Are T-Type Calcium Channel (CaV3) Inhibitors.
TLDR
Despite detections of MEPIRAPIM and 5F-BEPirAPIM in the NPS market, only the highest MEPIR APIM dose elicited a mild hypothermic response in mice, with no hypothermia observed for 5F/kg, suggesting minimal central CB1 receptor activity.
Defining Steric Requirements at CB1 and CB2 Cannabinoid Receptors Using Synthetic Cannabinoid Receptor Agonists 5F-AB-PINACA, 5F-ADB-PINACA, PX-1, PX-2, NNL-1, and Their Analogues.
TLDR
In vitro binding affinities and functional activities at cannabinoid type 1 and 2 receptors (CB1 and CB2, respectively) were determined for all the library members using radioligand competition experiments and a fluorescence-based membrane potential assay, providing insights regarding structural contributions to the cannabimimetic profiles of 17, 18, 19, and 20.
Study on the metabolic process of synthetic cannabinoids 4F-MDMB-BINACA and 4F-MDMB-BICA in human liver microsome and zebrafish model via UHPLC-QE Orbitrap MS
TLDR
These two structurally similar synthetic cannabinoids 4F-MDMB-BINACA and 4f-MD MB-BICA had similar metabolic processes, as well as similar structures of their main symbol metabolites.
Assessment of select synthetic cannabinoid receptor agonist bias and selectivity between the type 1 and type 2 cannabinoid receptor
TLDR
Assessment of select SCRAs recently identified by Canadian police, border service agency, private companies and the illicit market as potential CB1R and CB2R agonists provides initial insight into the correlations between structure, signalling bias, and in vivo activity of the SCRA.
NNL-3: A Synthetic Intermediate or a New Class of Hydroxybenzotriazole Esters with Cannabinoid Receptor Activity?
TLDR
The synthesis of NNL-3 analogues proved simple and general, and some of these showed potent cannabimetic profiles in vitro, indicating that HOBt esters of this type may represent an emerging class of SCRA NPS.
New synthetic cannabinoids carrying a cyclobutyl methyl side chain: Human phase-I metabolism and data on human cannabinoid receptor 1 binding and activation of Cumyl-CBMICA and Cumyl-CBMINACA.
TLDR
It is confirmed that substitution of an indole by an indazole core tends to increase in vitro potency which is potentially reflected by higher in vivo potency.
Induction of Liver Size Reduction in Zebrafish Larvae by the Emerging Synthetic Cannabinoid 4F-MDMB-BINACA and Its Impact on Drug Metabolism
TLDR
Investigating the metabolism of methyl 2-[1-(4-fluorobutyl)-1H-indazole-3-carboxamido]-3,3-dimethylbutanoate in ZF larvae after direct administration of the cannabinoid via microinjection revealed important insights into the in vivo metabolism of these compounds and the role of cannabinoid receptor binding.
Fatal intoxication with new synthetic cannabinoids 5F-MDMB-PICA and 4F-MDMB-BINACA—parent compounds and metabolite identification in blood, urine and cerebrospinal fluid
TLDR
Ester hydrolysis and oxidative defluorination products can be found in blood, urine and cerebrospinal fluid making them useful biomarkers of intake.
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References

SHOWING 1-10 OF 51 REFERENCES
Molecular and Behavioral Pharmacological Characterization of Abused Synthetic Cannabinoids MMB- and MDMB-FUBINACA, MN-18, NNEI, CUMYL-PICA, and 5-Fluoro-CUMYL-PICA
TLDR
This study demonstrates that novel structures being sold and used illicitly as substitutes for cannabis are retaining high affinity at the CB1 receptor, exhibiting greater efficacy than THC, and producing THC-like effects in models relevant to subjective effects in humans.
Pharmacology of Valinate and tert-Leucinate Synthetic Cannabinoids 5F-AMBICA, 5F-AMB, 5F-ADB, AMB-FUBINACA, MDMB-FUBINACA, MDMB-CHMICA, and Their Analogues.
TLDR
In vitro and in vivo data indicate that these SCs act as highly efficacious CB receptor agonists with greater potency than Δ(9)-THC and earlier generations of SCs.
Synthesis and pharmacology of new psychoactive substance 5F-CUMYL-P7AICA, a scaffold- hopping analog of synthetic cannabinoid receptor agonists 5F-CUMYL-PICA and 5F-CUMYL-PINACA.
TLDR
Five scaffold-hopping SCRAs, including 5F-CUMYL-P7AICA, were synthesized and characterized and found to exert potent cannabimimetic effects in mice, inducing hypothermia through a CB1 -dependent mechanism.
The next generation of synthetic cannabinoids: Detection, activity, and potential toxicity of pent-4en and but-3en analogues including MDMB-4en-PINACA.
TLDR
Results from toxicology testing paired with case history show the potential for MDMB-4en-PINACA to cause or contribute to impairment or death and Forensic scientists, public health and public safety officials, law enforcement, clinicians, medical examiners, and coroners should consider involvement of emergent synthetic cannabinoids in their work and that new analogues containing an alkene tail can retain similar or increased potency and toxicity.
Effects of bioisosteric fluorine in synthetic cannabinoid designer drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135.
TLDR
In vitro functional activities of SC designer drugs JWH-018, UR-144, PB-22, and APICA, and their respective terminally fluorinated analogues and in vivo in vivo cannabinoid type 1 receptor binding affinity evaluated in rats showed no consistent trend for increased potency of fluorinated SCs over the corresponding des-fluoro SCs in vivo.
Application of an activity-based receptor bioassay to investigate the in vitro activity of selected indole- and indazole-3-carboxamide-based synthetic cannabinoids at CB1 and CB2 receptors.
TLDR
Investigating the in vitro potency of 14 indole- and indazole-based SCs by applying a stable CB1 or CB2 receptor activation assay and correlating the activity with their structure confirmed how small differences in the structure of SCs might lead to large differences in their activity, especially at CB1, which may be correlated with differences inTheir toxic effects in humans.
Pharmacological evaluation of new constituents of “Spice”: synthetic cannabinoids based on indole, indazole, benzimidazole and carbazole scaffolds
TLDR
All compounds showed high CB receptor selectivity, mostly interacting with both subtypes, CB1 and CB2, and will be useful to assess the compounds’ toxicological risks and to guide legislation.
Enantiospecific Synthesis, Chiral Separation, and Biological Activity of Four Indazole-3-Carboxamide-Type Synthetic Cannabinoid Receptor Agonists and Their Detection in Seized Drug Samples
TLDR
A method to compare potency between samples containing different SCRAs at varying concentrations was developed and applied in this small preliminary study and provides a simplified method for assessing and communicating the risk of their use.
Pharmacology of Cumyl-Carboxamide Synthetic Cannabinoid New Psychoactive Substances (NPS) CUMYL-BICA, CUMYL-PICA, CUMYL-5F-PICA, CUMYL-5F-PINACA, and Their Analogues.
TLDR
Hypothermia was reversed by pretreatment with a CB1, but not CB2, antagonist, confirming that cumyl-derived SCs are cannabimimetic in vivo.
Shape Matters: The Application of Activity-Based In Vitro Bioassays and Chiral Profiling to the Pharmacological Evaluation of Synthetic Cannabinoid Receptor Agonists in Drug-Infused Papers Seized in Prisons.
TLDR
The importance of SCRA-CB1 receptor interactions in the 'head' or 'linked group' moiety is demonstrated, with the conformation of the 'bulky' tert-leucinate group greatly affecting potency, significantly greater than the difference observed between valinate SCRA enantiomers.
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