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Chemical Structure| 173600-10-7 Chemical Structure| 173600-10-7

Structure of 173600-10-7

Chemical Structure| 173600-10-7

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Product Citations

Product Citations

Janssens, Liesl K ; Ametovski, Adam ; Sparkes, Eric ; Boyd, Rochelle ; Lai, Felcia ; Maloney, Callan J , et al.

Abstract: Over 200 synthetic cannabinoid receptor agonists (SCRAs) have been identified as newpsychoactive substances. EffectivemonitoringandcharacterizationofSCRAsarehindered by the rapid pace of structural evolution. Ahead of possible appearanceontheillicitdrugmarket,newSCRAsweresynthesized tocompletea systematic libraryof cumyl-indole-(e.g.,CUMYL CPrMICA,CUMYL-CPMICA)andcumyl-indazole-carboxamides (e.g.,CUMYL-CPrMINACA,CUMYL-CPMINACA), encompass ing butyl, pentyl, cyclopropylmethyl, cyclobutylmethyl, cyclo pentylmethyl, andcyclohexylmethyl tails.Comprehensivepharma cologicalcharacterizationwasperformedwiththreeassayformats, monitoring the recruitment of either wild-type or C-terminally truncated(βarr2d366)β-arrestin2totheactivatedcannabinoid1 receptor(CB1)ormonitoringGβγ-mediatedmembranehyperpolarization.Alteredcompoundcharacterizationwasobservedwhen comparingderivedpotency(EC50)andefficacy(Emax)values frombothassaysmonitoringthesameoradifferentsignalingevent, whereasrangesandrankingordersweresimilar.Structure−activityrelationships(SAR)wereassessedinthreefold, resultinginthe identificationof thependant tailasacriticalpharmacophore,withtheoptimalchainlengthforCB1activationapproximatingann pentyl (e.g., cyclopentylmethyl or cyclohexylmethyl tail). The activityof the SCRAs encompassing cyclic tails decreasedwith decreasingnumberofcarbonsformingthecyclicmoiety,withCUMYL-CPrMICAshowingtheleastCB1activityinallassayformats. The SARs were rationalized viamolecular docking, demonstrating the importance of the optimal steric contributionof the hydrophobictail.WhileSARconclusionsremainedlargelyunchanged, thedifferential compoundcharacterizationbybothsimilar anddifferentassaydesignsemphasizestheimportanceofdetailingspecificassaycharacteristicstoallowadequateinterpretationof potenciesandefficacies.

Keywords: structure−activity relationship ; functional assays ; membrane potential ; βarrestin2 recruitment ; new psychoactive substances ; molecular docking

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Product Details of [ 173600-10-7 ]

CAS No. :173600-10-7
Formula : C12H12N2O2
M.W : 216.24
SMILES Code : O=C(C1=NN(CC2CC2)C3=C1C=CC=C3)O
MDL No. :MFCD20085246
Boiling Point : No data available

Safety of [ 173600-10-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338
 

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