Amine structure-activity relationships

Greim, H., H. J. Klimisch, M. Deben-Negele, and K. Ziegler-Skylakakis. 1998. Toxicity of aliphatic amines structure-activity relationship. Chemosphere 36(2) 271-95... 

In designing studies of the structure-activity relationships of MDMA and related substances, there are at least three areas for structural modification. First, the nature of the amine substituents can be varied other N-alkyls can be studied, or the nitrogen can be incorporated into a ring system. A second point for structural modification is the side chain. As already demonstrated, the alpha-methyl can be extended to an alpha-ethyl. Other modifications of the side chain would include incorporation into a variety of ring systems, or a,a-dialkylation. Finally, the nature and location of the ring substituents can be modified. 

Perhaps the advantage of the medicinal chemistry route lies in the flexibility of introducing different alkyl groups on the primary amine through reductive amination on 2-aminoethyl indole 10 and hence allows access to various N, N-dialkyl tryptamine derivatives for structure-activity relationship (SAR) studies. 

The earliest structure-activity relationships indicated that the transplatinum geometry is inactive— significantly higher doses must be given before any therapeutic effect is seen. In 1991, it was reported that alteration of amine structure and the introduction of sterically hindered amines produced cytotoxicity similar to that of cisplatin.162 The first examples used planar amines and a variety of tra s-[PtCl2(L)(L )] compounds have been synthesized and evaluated ((21)-(26), Figure 12).163... 

Based on the foregoing discussion, it is possible to formulate some structure-activity relationships with respect to the behavioral properties of various trypt-amine derivatives. It should be noted that these structure-activity relationships are derived from the results of both human and animal studies. 

Because rodent populations world-wide were becoming resistant to the widely used Warfarin-type anticoagulant poisons, a search was initiated to find a rodenticide with a different mode of action one that would be effective against these resistant rodents. This search led to the discovery of the toxic nature of a family of diphenyl amines which act as uncouplers of oxidative phosphorylation. A structure-activity relationship (SAR) study was undertaken to choose a derivative that would be both poisonous to rodents but still readily consumed by them. This approach led to the discovery of bromethalin,... 

Abstract The reversible reaction of primary or secondary amines with enolizable aldehydes or ketones affords nncleophilic intermediates, enamines. With chiral amines, catalytic enantioselective reactions via enamine intermediates become possible. In this review, structure-activity relationships and the scope as well as cnrrent limitations of enamine catalysis are discnssed. 

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