a, b, c, d, e represent diethylamine methyl, dimethylamine methyl, pyrrolidinyl methyl, piperidinyl methyl, morpholino methyl substituted in the position 2 of xanthone, respectively.
The influence order could be summarized as follows: diethylamine methyl ≈ dimethylamine methyl > pyrrolidinyl methyl > piperidinyl methyl > morpholino methyl against a-cetylcholinesterase activity and diethylamino methyl > pyrrolidinyl methyl > piperidinyl methyl > dimethylamine methyl > morpholino methyl against butyrylcholinesterase activity.
This interpretation was supported by observation of the TM-PaDDAH-dependent production of l-citrulline and methyl- or dimethylamine in the one-dimensional H NMR spectrum.
The results are shown in Table 1 and depicted in Figure 2. As seen in Table 1, coupling is favored for Grignard reagents with electron-donating substituents (dimethylamine, methoxy, and methyl), whereas electron-withdrawing substituents (chloride, fluoride, and trifluoromethyl) inhibit the coupling reaction.
For this study we used the following groups: methyl, acetyl, N,N-dimethylcarbamoyl, N,N-dimethylamine, N,N-diethylamine, piperidine, pyrrolidine, and N,N-methylbenzylamine.
They contain an electron-rich group (dimethylamine) located on the methyl moiety, which may confer a better stability to the molecule in vivo.
An attempt to prepare 10a directly from the methyl ester intermediate 9 upon treatment with dimethylamine under microwave irradiation resulted in formation of the corresponding carboxylic acid.
MN58b (1,4-[4-4′-Bis-{[4- dimethylamine) pyridinium-1,4-[4-4′-Bis-{[4- dimethylamineibromide) has demonstrated potent antiproliferative and antitumoral activity in vivo.
A similar compound, chlortetracycline, which only differs from minocycline by the addition of a hydroxyl and methyl group at position 6 and a chloro group replacing the dimethylamine moiety at position 7, is a significantly more potent inhibitor (Ki value of ∼0.11 mM).
