Antiparkinsonian activity of some 9-N-, O-, S- and C-derivatives of 3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol

• Published in: Bioorganic & medicinal chemistry 2013-03, Vol.21 (5), p.1082-1087
• Main Authors: Ardashov, Oleg V., Pavlova, Alla V., Korchagina, Dina V., Volcho, Konstantin P., Tolstikova, Tat’yana G., Salakhutdinov, Nariman F.
• Format: Article
• Language: English
• Subjects: (1R,2R,6S)-3-Methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol; animal models; Animals; Antiparkinson Agents - chemistry; Antiparkinson Agents - pharmacology; Antiparkinson Agents - therapeutic use; Antiparkinsonian activity; Basal ganglia; chemistry; Cyclohexanols - chemistry; Cyclohexanols - pharmacology; Cyclohexanols - therapeutic use; Derivatives; Disease Models, Animal; locomotion; Male; Mice; Mice, Inbred C57BL; Monoterpenoid; Motor Activity - drug effects; MPTP model; MPTP Poisoning - chemically induced; MPTP Poisoning - drug therapy; nitrogen; Stereoisomerism
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2013.01.003

Earlier it was found, that (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol (1) possess high antiparkinsonian activity. The N-, O-, S- and C-derivatives at the C-9 position of diol 1 were synthesized in this work. The antiparkinsonian activity of these compounds was studied in MPTP mice models. As a rule, the introduction of substituents containing nitrogen atoms at the C-9 position led to a considerable decrease or loss of antiparkinsonian activity. A derivative of 2-aminoadamantane 8 significantly decreased the locomotor activity time, thus enhancing the symptoms of the parkinsonian syndrome. However the introduction of butyl or propylthio substituents at the C-9 position of diol 1 did not diminish the antiparkinsonian activity comparing to parent compound. This information is important when choosing a route for immobilization of compound 1 to find possible targets.