Deprotonation Equilibrium of 5‑Tropolonediazonium Salt Strongly Favors 1,2,5-Tropoquinone-5-diazide Structure in Certain Solvents

5-Tropolonediazonium salt <b>1</b> is a well-known intermediate for the preparation of 5-substituted tropolone derivatives, but 1,2,5-tropoquinone-5-diazide <b>2</b>, which is expected to be formed by deprotonation of <b>1</b>, has not been reported. We synthesized <b>2</b>, and the structures of <b>1</b> and <b>2</b> were investigated and compared. NMR and UV spectral data indicated that <b>1</b> is easily deprotonated in water, methanol, DMSO, and DMF and exists in the form of <b>2</b> in these solvents (but not in acetone or acetonitrile) because of its strong acidity (estimated p<i>K</i>_a −2.07). Thus, the acid–base equilibrium shows strong solvent-dependence. Compound <b>2</b> may be synthetically available as a carbene precursor

Silicon-Containing GABA Derivatives, Silagaba Compounds, as Orally Effective Agents for Treating Neuropathic Pain without Central-Nervous-System-Related Side Effects

Neuropathic pain is a chronic condition resulting from neuronal damage. Pregabalin, the (<i>S</i>)-isomer of 3-isobutyl-γ-aminobutyric acid (GABA), is widely used to treat neuropathic pain, despite the occurrence of central nervous system (CNS)-related side effects such as dizziness and somnolence. Here we describe the pharmacology of novel GABA derivatives containing silicon–carbon bonds, silagaba compounds. Silagaba131, 132, and 161 showed pregabalin-like analgesic activities in animal models of neuropathic pain, but in contrast to pregabalin they did not impair neuromuscular coordination in rotarod tests. Pharmacokinetic studies showed that brain exposure to silagaba compounds was lower than that to pregabalin. Surprisingly, despite their potent analgesic action in vivo, silagaba compounds showed only weak binding to α2-δ protein. These compounds may be useful to study mechanisms of neuropathic pain. Our results also indicate that silagaba132 and 161 are candidates for orally effective treatment of neuropathic pain without CNS-related side effects