Phenylalkylamines of Potential Biological Interest

  • J.S. Dowrick

Student thesis: Doctoral ThesisDoctor of Philosophy


As a result of a preliminary biological screen certain basic compounds containing a tricyclic system in which one of the rings was heterocyclic were found to exhibit antiviral activity against both DNA and RNA type viruses.

Certain other basic compounds containing two phenyl groups connected to the same carbon atom and separated from the basic group by a methylene chain also appeared to have this activity. At the outset it was realised that compounds o* this nature might also exhibit useful pharmacological activity

In the present investigation it was thought desirable to prepare compounds of the general type: <IMAGE> and possibly to further investigate the structure activity relationships by preparing analogues of the type <IMAGE> where Z = N or C, and X is a bridging group.

During the present investigation compounds of the following types were prepared, the first being of the general formula <FORMULA> where X = CN, H, or CoH; and NR,R, = dimethylamino, morpholino, These were synthesised by the condensation of diphenylacetonitrile with the appropriate chloro-amine, and removal of the cyano group with sodamide. One of the Seat rings was selectively reduced by a catalytic hydrogenation, steric factors playing a role. Several of these compounds showed promising antiviral activity.

A closely related series <IMAGE> where R1 = phenyl, cyclohexyl, methyl, n-butyl, p-tolyl. R3 = methyl, ethyl, n- butyl; R2= methyl, 2-hydroxyethyl;
were synthesised by modified Grignard, aryl-lithium, or alkyllithium
addition to the appropriate Mannich bases.

Methods of amination of Mannich bases were investigated, either by reductive amination or by isolation of their yada to provide a facile route for the synthesis of a further series of compounds: <IMAGE> where R1= an alkyl or acyl group
R2= methyl or 2-hydroxyethyl.

The synthetic route adopted was that of alkylation or acylation of the diamine resulting from reduction of the oxime of the Mannich base.

The lability of the terminal dialkylamino group was noted, and the ability of this series to undergo ring closure was demonstrated.

A substantial number of these compounds were assessed for antiviral and other pharmacological activity.
Date of Award1970
Original languageEnglish

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