Dimethylpiper azine

Dipole-moment measurements in benzene solution on 1,4-dimethylpiper-azine and on a series of 1 -alkyl-4-tm-butylpiperazines120 show clearly that the N-alkyl groups exist predominantly in the expected position and indicate a value of 1.8 kcal mol-1 for the N-methyl group. This must now be considered a minimum value, and kinetic protonation of 1,4-dimethylpiperazine with 13C-NMR analysis of the products326 gives 2.96 + 0.05 kcal mol". An attempt312 to apply the line-broadening method failed.313... 

Within the series of compounds containing the (25 ,52 )-dimethylpiper-azine, there is not always a preferred benzhydryl epimer. The epimer with R stereochemistry at this position was certainly preferred for BW373U86 with respect to delta opioid receptor agonism, but for other compounds there was little difference in the activity of the epimers. For example, pyridine containing compounds 35 and 36 have similar potencies at the delta and mu opioid receptors (Table 4). As demonstrated by the activity of related compounds (see Sec. 2.3), the stereochemical features of (+)-BW373U86 are not essential to the delta opioid receptor pharmacophore. 

---