The effect of 3,7-diazabicyclo[3.3.1]nonanescontaining monoterpenoid moieties on the physical activity of mice.

Abstract

The aim of this work is to study the effect of agents combining fragments of monoterpenoids and 3,7diazabicyclo[3.3.1]nonane (bispidine) on the performance of mice. Physical endurance was studied using two tests: exhaustive swimming with a load of 7% of body weight (after single dosing) and exhaustive treadmill running (after single dosing and a 7-day administration). It has been shown for the first time that derivatives of monoterpenoids with 3,7-diazabicyclo[3.3.1]nonane moiety containing methyl substituents at positions 1 and 5 have a stimulatory effect on the performance of mice, which exceeds the effect of the reference drug bromantane after single dosing. Compound K1-458, which contains (-)-myrtenal residues linked to a bispidine fragment via amino groups, is the most effective in increasing the duration of running and swimming at a dose of 100 mg/kg after single intragastric administration. It has been also established that the LD50 for these compounds exceeds 1,000 mg/kg.

Bispidine Platform as a Tool for Studying Amide Configuration Stability

“…The chiral bis-amide 1g was obtained by the interaction of the acid chloride of (1R)-(−)-myrtenic acid obtained from (-)-myrtenol with diazaadamantanone in a water-benzene mixture in the presence of NaHCO 3 (Scheme 6). The effect of the compound on the physical activity of mice was recently studied [37]. Moreover, 1g was used as a ligand of metal complex catalysts for the Henry reaction [34].…”

“…The assignment of the signals in the NMR spectra of 1g in CDCl 3 was carried out using 2D experiments (COSY, NOESY, HSQC, HMBC, see SI) and generally coincides with that in [37], with the exception of protons and carbon atoms of the bispidine framework (the assignment in that work was not fulfilled completely). We performed full assignment of all signals for 1g in CDCl 3 and DMSO-d 6 in which VT experiments were carried out.…”