It's all things adamantane in our (@Lambert_Usyd) latest synthetic cannabinoid work, out now in @ACSChemNeurosci!. We synthesised and evaluated a library of adamantane-derived SCRAs, including fluorinated and deuterated analogues 🧪.🧵.

RT @christophestove: 🎤 presentation by @AxelleTimmerman @ #TIAFT2024:."Synthesis and functional evaluation of synthetic cannabinoid recepto….

RT @callanmaloney01: Great to see this one finally out there, and even better to have worked with the awesome team at @Lambert_Usyd back in….

Support from @Lambert_Usyd, @SydneyChemistry, @Sydney_Science, Sydney Pharmacy School, @syd_health + ANSTO.

And to @samuel_b_phd, @EA_Cairns and @AdamAmetovski for overseeing this work!.

Thanks to all coauthors for their work: @callanmaloney01, @JackMarkhamPhD, Chianna Dane, Rochelle Boyd, Jayson Gilchrist, Michael Moir, Rebecca Gordon, Jia Lin Luo, @Ed_Pike, Katelyn Walker, Michael Kassiou, @iainsmcgregor, @RichardKevinPhD, Dai Hibbs and @WillJorgo.

As always, SAR was used to rationalise observed SAR at CB1 and CB2. @JackMarkhamPhD + Dai Hibbs

Bridgehead fluorination and perdeuteration of the adamantane moiety tended to result in lower activity, with the effect being more pronounced at CB1 than at CB2

Indazole derivatives reigned supreme at CB1, with CB2 being more tolerant to changes in the scaffold. Rochelle Boyd, Katie Walker and @EA_Cairns

We synthesised a series of indole, indazole, and 7-azaindole-3-carboxamides, containing the classic adamantane SCRA head group + deuteration + fluorination . @callanmaloney01, Chianna Dane + Jayson Gilchrist (@KassiouGroup), Michael Moir, Jia Lin Luo, @ed_pike + @AdamAmetovski

RT @christophestove: Nice collaborative work (1st paper of @AxelleTimmerman 👏) w. @eric_sparkes & other fantastic @Lambert_Usyd colleagues….

Thanks to @Lambert_Usyd, @SydneyChemistry, @Sydney_Science, @BrainMind_Usyd, @MQMedicalSchool, and Sydney Pharmacy School for making this work possible.

Amazing team includes @JackMarkhamPhD, Rochelle Boyd, @TheCannabisGuyy, Humayra Zaman, Rebecca Gordon, Katelyn Walker, Chianna Dane (@KassiouGroup), @RichardKevinPhD, @MariJSantiago, Dai Hibbs, @samuel_b_phd, @AdamAmetovski, and @EA_Cairns.

Induced fit docking was used to rationalise observed SAR, performed by @JackMarkhamPhD and Dai Hibbs.

Functional evaluation was carried out by @EA_Cairns, @TheCannabisGuyy, @MariJSantiago, Rochelle Boyd, and Humayra Zaman, measuring agonism through G protein dependent signaling. Varied activity between enantiomers was observed at CB1 and CB2.

We synthesised and characterised a series of indole-3-carboxamides related to detected SCRAs MPP-5F-PICA, MMB-5F-PICA, and MDMB-5F-PICA, branching out from the typical valinyl and tert-leucinyl derived head groups. Both natural configurations and enantiomers were investigated.

More SCRA work from @Lambert_Usyd out now in @rsc_medchem!. We looked at a series of proteinogenic amino acid-derived SCRAs related to MPP-5F-PICA, MMB-5F-PICA, and MDMB-5F-PICA, investigating the role of chirality in CB1 and CB2 receptor activation.

Thanks to @Lambert_Usyd @SydneyChemistry @Sydney_Science @ugent and Sydney Pharmacy School for the ongoing support.

Amazing team includes @AxelleTimmerman @JackMarkhamPhD Rochelle Boyd, Rebecca Gordon, Katelyn Walker, @RichardKevinPhD, Dai Hibbs, @samuel_b_phd, @EA_Cairns, @christophestove, and @AdamAmetovski ✨✨.

In silico evaluation was used to rationalise some structure-activity relationships observed with Induced fit docking performed by @JackMarkhamPhD and Dai Hibbs