(1R,2R,6S)-2-(1H-1,2,4-Triazol-3-ylthio)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-enol as promising molecule able to support the survival of primary cultured dopamine neurons

Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with motor symptoms (tremor, rigidity, etc.) as well as cognitive and behavioral problems. Nowadays, Levodopa, the main drug for Parkinson’s disease treatment, has serious side effects, including forgetfulness, headache, etc. For that reason, development of new drug for effective treatment of PD is extremely important. Recently, it was found in Novosibirsk Institute of Organic Chemistry that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol (1) demonstrated high anti-Parkinsonian activity in vivo on animal models in mice and rats.

Subsequently, several modifications of 1 at different sites were carried out. Although most modifications led to decrease in activity, a few new compounds demonstrated promising anti-Parkinsonian activity. Here, we present stereoselective synthesis of (1R,2R,6S)-2-(1H-1,2,4-triazol-3-ylthio)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-enol (2) with the same stereochemistry of all asymmetric centers as in parent compound 1. It was shown that derivative 2 demonstrates high anti-PD in mice MPTP and haloperidol models of Parkinson’s disease as well as restoration of dopamine concentration in midbrain.