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UBC Theses and Dissertations

Investigation of homo- and hetero-aromatic analogues of cyclohexyl substituted Antergan for pharmacological activities Wang, Stanley Yih Song


In the present study seven tertiary ethylenediamine derivatives were synthesized. They had the basic structure of N.N-dimethyl-N'-R₁-N'-R₂-ethylenediamine where R₁ = cyclohexyl-methyl and R₂ = 2-pyridyl, 2-pyrimidyl, 2-pyrazyl, 1-naphthyl, 5-quinolyl; and R₁ = cyclohexanecarbonyl and R₂ = 2-pyrimidyl, 2-pyrazyl. Two oxetane derivatives, 2,2-diphenyl-3-chloro-oxetane and 2,2-diphenyl-3-(pyrrolidin-2-one-1-yl)oxetane, have also been synthesized as intermediates for further investigation. The general reaction sequence followed was to start with the appropriate primary aromatic amine and build up to a secondary amine via a cyclohexanecarboxamide. The desired secondary amine was reacted with β-dimethylaminoethyl chloride. The tertiary diamine readily formed in good yields. In cases where the primary aromatic amines could not be built up to a secondary amine via the above route, the tertiary diamine derivative was obtained by two condensation reactions, i.e. the primary aromatic amine was first condensed with β-dimethyl-aminoethyl chloride to form the desired secondary amine which was then condensed with cyclohexylmethyl bromide to produce the tertiary diamine derivative. The overall yields were lower than those of the first route. The oxetane derivatives were obtained by photocyclo-addltion of benzophenone to either vinyl chloride or N-vinyl-2-pyrrolidinone. The antihistaminic activity and the possible anticholinergic activity of the tertiary diamine derivatives were studied and compared with those of diphenhydramine, atropine, and the cyclohexyl analogue of Antergan. These compounds exhibited negligible anticholinergic activity. However, their relatively potent antihistaminic activity was found to give more evidence In direct support of Nauta’s antihistaminic receptor theory.

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