ABSTRACT
Solid-state 13C and 19F NMR spectroscopy offers a non-destructive, highly selective protocol for the identification of forensically relevant synthetic cannabinoids on herbal substrates. Using this technique, well resolved 13C spectra were obtained that readily enabled structural identification; in some instances complemented by 19F spectral data. The approach described has potential for related applications such as the direct detection of pesticides on plants.
Subject(s)
Cannabinoids/analysis , Designer Drugs/analysis , Nuclear Magnetic Resonance, Biomolecular/methods , Plant Preparations/chemistry , Turnera/chemistry , Cannabinoids/chemistry , Designer Drugs/chemistry , Molecular StructureABSTRACT
Robust methodology to install amide, carbamate, urea and sulfonamide functionality to the 1,8-naphthalimide scaffold has been developed and exemplified. New benzamidonaphthalimide 6, synthesised using this approach, was found to be sensitive to base whereupon fluorescence emission strongly increases (>10-fold) and red-shifts (>4000 cm-1). The optical properties of deprotonated 6 allow for single molecule fluorescence detection, the first example of such behaviour from this class of fluorophore.
ABSTRACT
Adenosines bearing 5'-modification in conjunction with an N6-substituent have previously been shown to act as partial agonists at the A1 adenosine receptor. Our current work investigates the effect of modifying the 5'-position in conjunction with efficacious bicyclic and tricyclic N6-substituents. Several highly potent agonists for the A1 adenosine receptor were identified; however, all of these compounds behaved as full agonists. In keeping with previous reports, 5'-halogen and 5'-sulfide derivatives of N6-(endo-norborn-2-yl)adenosine were, in general, low nanomolar agonists of the A1 adenosine receptor. The known partial agonist, N6-cyclopentyl-5'-deoxy-5'-ethylthioadenosine (2), also behaved as a full agonist in our assay.
Subject(s)
Adenosine A1 Receptor Agonists , Adenosine/analogs & derivatives , Adenosine/pharmacology , Adenosine/chemistry , Heterocyclic Compounds, 2-Ring , Heterocyclic Compounds, 3-Ring , Humans , Structure-Activity RelationshipABSTRACT
Two series of N(6)-substituted adenosines with monocyclic and bicyclic N(6) substituents containing a heteroatom were synthesized in good yields. These derivatives were assessed for their affinity ([(3)H]CPX), potency, and intrinsic activity (cAMP accumulation) at the A(1) adenosine receptor in DDT(1) MF-2 cells. In the monocyclic series, the N(6)-tetrahydrofuran-3-yl and thiolan-3-yl adenosines (1 and 26, respectively) were found to possess similar activities, whereas the corresponding selenium analogue 27 was found to be more potent. A series of nitrogen containing analogues showed varying properties, N(6)-((3R)-1-benzyloxycarbonylpyrrolidin-3-yl)adenosine (30) was the most potent at the A(1)AR; IC(50)=3.2 nM. In the bicyclic series, the effect of a 7-azabicyclo[2.2.1]heptan-2-yl substituent in the N(6)-position was explored. N(6)-(7-Azabicyclo[2.2.1]heptan-2-yl)adenosine (38) proved to be a reasonably potent A(1) agonist (K(i)=51 nM, IC(50)=35 nM) while further substitution on the 7''-nitrogen with tert-butoxycarbonyl (31, IC(50)=2.5 nM) and 2-bromobenzyloxycarbonyl (34, IC(50)=9.0 nM) gave highly potent A(1)AR agonists.
Subject(s)
Adenosine/chemistry , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/pharmacology , Adenosine/pharmacology , Heterocyclic Compounds/chemistry , Inhibitory Concentration 50 , Molecular Structure , Purinergic P1 Receptor Agonists , Structure-Activity RelationshipABSTRACT
Herein we report a short and efficient synthesis of N(6)-substituted 5'-modified adenosines, which was achieved in four steps from 2',3',5'-tris-O-(tert-butyldimethylsilyl)inosine.