Design, synthesis and pharmacological profile of (−)-verbenone hydrazones

A series of novel (−)-verbenone hydrazones was designed and synthesized via condensation of terpenoid with hydrazides derived from phenoxyacetic acid. The structure of target compounds was confirmed by 1H-NMR and 13C-NMR analysis, Raman and FT-IR spectroscopy, electrospray ionization method and fast atom bombardment (FAB) mass spectrometry. Thermal properties of (−)-verbenone hydrazones 3a–3e were estimated by differential scanning calorimetry and their purity by HPLC coupled to mass spectrometry. Verbenone hydrazones were revealed to exist as Z/E geometrical isomers about C═N bond and cis/trans amide conformers. Verbenone derivatives were estimated as potential anticonvulsant agents after their oral administration against pentylenetetrazole and maximal electroshock-induced seizures in mice. Analgesic effect of hydrazones was studied by topical application on models of allyl isothiocyanate and capsaicin-induced pain. The present findings indicate that verbenone hydrazones contribute to seizure protection both at short (6 h) and long (24 h) time periods by blocking chemical- and electroshock-induced convulsions. Binding of compounds 3a–3e to TRPA1/TRPV1 ion channels was suggested as a feasible mechanism explaining their significant analgesic activity.

(2S,5R)-2-Isopropyl-5-methylcyclohexanone Hydrazones

Hydrazones were obtained in 76–78% yield via condensation of (2S,5R)-2-isopropyl-5-methylcyclohexanone with 4-R-phenoxyacetic acid hydrazides in the presence of a catalytic amount of glacial acetic acid. The structure of the target compounds has been established by FTIR-ATR, Raman, 1H-NMR and 13C-NMR spectral analysis and EI/FAB/ESI mass spectrometry. Thermal properties of hydrazones 3a–3e were elucidated by differential scanning calorimetry (DSC) and their purity by HPLC coupled to mass spectrometry. Synthesized compounds were found to exist as Z/E geometrical isomers about C=N bond and cis/trans amide conformers.

Synthesis and Conformational Assignment of N-(E)-Stilbenyloxymethylenecarbonyl-Substituted Hydrazones of Acetone ando-(m- andp-) Chloro- (nitro-) benzaldehydes by Means of and NMR Spectroscopy

Eighteen new N-(E)-stilbenyloxyalkylcarbonyl-substituted hydrazones ofortho- (meta- andpara-) chloro- (nitro-) benzaldehydes1–18and two analogous hydrazones of acetone19-20were prepared. The stereochemical behavior of1–18in dimethyl-d6sulfoxide solution has been studied by NMR and NMR techniques, using spectral data of19and20as supporting material. The E-geometrical isomers and cis-/trans-amide conformers have been found for these hydrazones. Energy barriers of isomers are reported.