Development of Imidazole-Reactive Molecules Leading to a New Aggregation-Induced Emission Fluorophore Based on the Cinnamic Scaffold

In order to obtain new fluorophores potentially useful in imidazole labeling and subsequent conjugation, a small series of Morita–Baylis–Hillman acetates (<b>3a–c</b>) was designed, synthesized, and reacted with imidazole. The optical properties of the corresponding imidazole derivatives <b>4a–c</b> were analyzed both in solution and in the solid state. Although the solutions display a very weak emission, the powders show a blue emission, particularly enhanced in the case of compound <b>4c</b> possessing two methoxy groups in the cinnamic scaffold. The photophysical study confirmed the hypothesis that the molecular rigidity of the solid state enhances the emission properties of these compounds by triggering the restriction of intramolecular motions, paving the way for their applications in fluorogenic labeling

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 ¹H- and ¹³C-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