Indol-2-Carboxylic Acid Esters Containing N-Phenylpiperazine Moiety - Preparation and Anticholinergic Activity.

BACKGROUND The indole derivatives and the N-phenylpiperazine fragment represent interesting molecular moieties suitable for the research of new potentially biologically active compounds. This study was undertaken to identify if indol-2-carboxylic acid esters containing N-phenylpiperazine moiety possess acetylcholinesterase and butyrylcholinesterase inhibitory activity. METHOD The study dealt with the synthesis of a novel series of analogs of 1H-indole-2-carboxylic acid and 3-methyl-1Hindole-2-carboxylic acid. The structure of the derivatives was represented by the indolylcarbonyloxyaminopropanol skeleton with the attached N-phenylpiperazine or diethylamine moiety, which formed a basic part of the molecule. The final products were synthesized as dihydrochloride salts, fumaric acid salts, and quaternary ammonium salts. The first step of the synthetic pathway led to the preparation of esters of 1H-indole-2-carboxylic acid from the commercially available 1H-indole-2- carboxylic acid. The Fischer indole synthesis was used to synthesize derivatives of 3-methyl-1H-indole-2-carboxylic acid. RESULTS Final 18 indolylcarbonyloxyaminopropanols in the form of dihydrochlorides, fumarates, and quaternary ammonium salts were prepared using various optimization ways. The compounds were evaluated for the selected anticholinergic activity by modified Ellman method. The relationship between their chemical structure and their biological effect was discussed. IN CONCLUSION Final 18 indolylcarbonyloxyaminopropanols in the form of dihydrochlorides, fumarates and QUATs were prepared, using various optimizing ways to synthesize the substances, and then thoroughly analyzed using available instrumental methods. Most of the derivatives were comprised of an attached N-phenylpiperazine group, which formed a basic part of the molecule and in which the fenyl ring was substituted in position C-2 or C-4. The synthesized compounds were subjected to selected anticholinergic activity evaluation, and thus the impacts of their chemical structure on their biological effect were discussed.