Collect. Czech. Chem. Commun. 1990, 55, 2304-2316

Potential cholinergic and anticholinergic compounds: Synthesis of 2,8-substituted 2,8-diazaspiro[4,5]decane-1,3-diones

Vladimír Valenta, Jiří Holubek, Emil Svátek and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, SPOFA, 130 60 Prague 3


Heating the ammonium salt of (4-carboxy-1-methyl-4-piperidinyl)acetic acid (XII) gave 8-methyl-2,8-diazaspiro[4,5]decane-1,3-dione (II) which was N-alkylated with 2-bromoethanol and 4-bromobutanol to give the alcohols III and V. Compound III was transformed to the chloro compound VI which was reacted with the sodium salt of hexahydrobenzilic acid to give the ester VII. Compound V was transformed to the 4-toluenesulfonic ester VIII which reacted with 1-(2-pyrimidinyl)piperazine and gave IX. 2-(2-Propyl)-2,8-diazaspiro[4,5]decane-1,3-dione (XVIII) was similarly transformed via XIX to XX which reacted with the sodium salts of diphenylacetic, benzilic, hexahydrobenzilic, and (2-oxo-1-pyrrolidinyl)acetic acid to give the esters XXI-XXIV. The esters VII and XXI-XXIV were transformed to the methiodides. The compounds prepared were tested in the lines of activity of the analogous "RS-86" (I) but proved inactive.