12 research outputs found
Synthesis of first acyclic trinuclear ruthenium(II) phenolate schiff base complex from acyclic tripodal and macrobicyclic ligands
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
Bridging and Terminal Half-Sandwich Ruthenium Dinitrogen Complexes and Related Derivatives: A Structural Study
Coordinatively Unsaturated Ruthenium Phosphine Half-Sandwich Complexes: Correlations to Structure and Reactivity
3′-Functionalized Adamantyl Cannabinoid Receptor Probes
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
Novel 1′,1′-Chain Substituted Hexahydrocannabinols: 9β-Hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol (AM2389) a Highly Potent Cannabinoid Receptor 1 (CB1) Agonist
Human Cannabinoid Receptor 2 Ligand-Interaction Motif: Transmembrane Helix 2 Cysteine, C2.59(89), as Determinant of Classical Cannabinoid Agonist Activity and Binding Pose
Controlled-Deactivation Cannabinergic Ligands
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