12 research outputs found

    Synthesis of first acyclic trinuclear ruthenium(II) phenolate schiff base complex from acyclic tripodal and macrobicyclic ligands

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    442-450An acyclic trinuclear ruthenium(II) Schiff base complex Ru3H3L1(DMSO)6Cl6, 1, has been isolated for the first time from preformed acyclic tripodal ligands H3L1, H3L2 and also from macrobicyclic ligand H3L3 instead of the dinuclear ruthenium complex 2. The ligand H3L1 crystallizes in space group R and exhibits carry over of molecular trigonal symmetry into crystal. Trigonal network is due to intermolecular interactions of aminomethylene (N-CH2) proton and formyl (CH=O) oxygen. The CSD analysis reveals that N-C-H... O=CH interaction is unique. The complex Ru3H3L1(DMSO)6Cl6 1 crystallizes in triclinic P space group. Each ruthenium atom is coordinated by phenolic and formyl oxygens of ligand, sulphur atoms of two DMSO moieties in equitorial plane and two chloride ions in axial positions providing distorted octahedral geometry. The Ru-Ru distances in complex 1 indicate that there is no interaction between the metal centers. Further reaction of complex 1 with tren and ruthenium metal does not yield macrobicyclic complex 2 showing the inertness of the coordinated formyl group towards Schiff base condensation. The electronic spectrum of the complex shows charge transfer bands while cyclic voltammetry in dichloromethane solvent gives a single reversible redox couple at E1/2 = 0.87 V (vs Ag-AgCl) corresponding to Ru(II) to Ru(III) oxidation

    3′-Functionalized Adamantyl Cannabinoid Receptor Probes

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    The aliphatic side chain plays a pivotal role in determining the cannabinergic potency of tricyclic classical cannabinoids, and we have previously shown that this chain could be substituted successfully by adamantyl or other polycyclic groups. In an effort to explore the pharmacophoric features of these conformationally fixed groups, we have synthesized a series of analogues in which the C3 position is substituted directly with an adamantyl group bearing functionality at one of the tertiary carbon atoms. These substituents included the electrophilic isothiocyanate and photoactivatable azido groups, both of which are capable of covalent attachment with the target protein. Our results show that substitution at the 3′-adamantyl position can lead to ligands with improved affinities and CB1/CB2 selectivities. Our work has also led to the development of two successful covalent probes with high affinities for both cannabinoid receptors, namely, the electrophilic isothiocyanate AM994 and the photoactivatable aliphatic azido AM993 analogues

    Controlled-Deactivation Cannabinergic Ligands

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    We report an approach for obtaining novel cannabinoid analogues with controllable deactivation and improved druggability. Our design involves the incorporation of a metabolically labile ester group at the 2′-position on a series of (−)-Δ<sup>8</sup>-THC analogues. We have sought to introduce benzylic substituents α to the ester group which affect the half-lives of deactivation through enzymatic activity while enhancing the affinities and efficacies of individual ligands for the CB1 and CB2 receptors. The 1′-(<i>S</i>)-methyl, 1′-<i>gem</i>-dimethyl, and 1′-cyclobutyl analogues exhibit remarkably high affinities for both CB receptors. The novel ligands are susceptible to enzymatic hydrolysis by plasma esterases in a controllable manner, while their metabolites are inactive at the CB receptors. In further in vitro and in vivo experiments key analogues were shown to be potent CB1 receptor agonists and to exhibit CB1-mediated hypothermic and analgesic effects
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