2 research outputs found
Flow Synthesis and Biological Studies of an Analgesic Adamantane Derivative That Inhibits P2X<sub>7</sub>‑Evoked Glutamate Release
We report the biological evaluation
of a class of adamantane derivatives,
which were achieved via modified telescoped machine-assisted flow
procedure. Among the series of compounds tested in this work, <b>5</b> demonstrated outstanding analgesic properties. This compound
showed that its action was not mediated through direct interaction
with opioid and/or cannabinoid receptors. Moreover, it did not display
any significant anti-inflammatory properties. Experiments carried
out on rat cerebrocortical purified synaptosomes indicated that <b>5</b> inhibits the P2X<sub>7</sub>-evoked glutamate release, which
may contribute to its antinociceptive properties. Nevertheless, further
experiments are ongoing to characterize the pharmacological properties
and mechanism of action of this molecule
Novel Analgesic/Anti-Inflammatory Agents: 1,5-Diarylpyrrole Nitrooxyalkyl Ethers and Related Compounds as Cyclooxygenase‑2 Inhibiting Nitric Oxide Donors
A series of 3-substituted 1,5-diarylpyrroles
bearing a nitrooxyalkyl
side chain linked to different spacers were designed. New classes
of pyrrole-derived nitrooxyalkyl inverse esters, carbonates, and ethers
(<b>7</b>–<b>10</b>) as COX-2 selective inhibitors
and NO donors were synthesized and are herein reported. By taking
into account the metabolic conversion of nitrooxyalkyl ethers (<b>9</b>, <b>10</b>) into corresponding alcohols, derivatives <b>17</b> and <b>18</b> were also studied. Nitrooxy derivatives
showed NO-dependent vasorelaxing properties, while most of the compounds
proved to be very potent and selective COX-2 inhibitors in in vitro
experimental models. Further in vivo studies on compounds <b>9a</b>,<b>c</b> and <b>17a</b> highlighted good anti-inflammatory
and antinociceptive activities. Compound <b>9c</b> was able
to inhibit glycosaminoglycan (GAG) release induced by interleukin-1β
(IL-1β), showing cartilage protective properties. Finally, molecular
modeling and <sup>1</sup>H- and <sup>13</sup>C-NMR studies performed
on compounds <b>6c</b>,<b>d</b>, <b>9c</b>, and <b>10b</b> allowed the right conformation of nitrooxyalkyl ester
and ether side chain of these molecules within the COX-2 active site
to be assessed