Martin Richard Teall

A new series of potent benzodiazepine γ-secretase inhibitors

Abstract A new series of benzodiazepine-containing γ-secretase inhibitors with potential use in the treatment of Alzheimers disease is disclosed. Structure–activity relationships of the pendant hydrocinnamate side-chain which led to the preparation of highly potent inhibitors are described.

Acyclic NK-1 antagonists: 2-benzhydryl-2-aminoethyl ethers

Abstract A series of 2-aminoethyl ethers based on diphenylalaninol have been shown to have significant affinity for the human NK 1 receptor and reduced affinity at the L-type Ca ++ channel compared with quinuclidines related to CP 96,345.

Acyclic NK1 antagonists: Replacements for the benzhydryl group.

Abstract An exploration of benzhydryl replacements is described. Whilst bridged and fused polynuclear aromatic systems both incur a reduction in affinity it was possible to replace the benzhydryl by a single phenyl ring with only a modest reduction in affinity. In contrast to the analogous diphenylalanyl ethers the binding was also shown to be stereoselective.

4-Heterocyclyl tetrahydropyridines as selective ligands for the human dopamine D4 receptor

Abstract A series of 1,2,3,6-tetrahydropyridines 3 were synthesised, which resulted in selective high affinity dopamine D4 ligands. The SAR of heterocyclic replacements and aromatic substitution was investigated, leading to compounds of nanomolar binding affinity with excellent selectivity over both D2 and D3 receptors.

4-hydroxyphenoxymethylene bisphosphonic acid derivatives: potent, non-hydrolysable inhibitors of MYO-inositol monophosphatase

Abstract From a series of 4-hydroxyphenoxymethylene bisphosphonic acid derivatives 1-(4-Hydroxyphenoxy)-1-(methyl)methylenebisphosphonic acid has been identified as a structurally simple, competitive, inhibitor of myo -inositol monophosphatase (IC 50 , 0.33 μM). Replacement of the 1-methyl group by a 3-(3,4-dichlorobenzamido)benzyl substituent affords the most potent inhibitor of the series (IC 50 , 0.08 μM).

Linear amides as substance P antagonists

Abstract In the present study we demonstrate that an amide linking group provides an excellent template for the positioning of a benzhydryl group and a suitably functionalized aromatic ring in an orientation which allows for high affinity binding to the hNK1 receptor.

Inhibitors of myo-inositol monophosphatase unrelated to the enzyme substrate

Abstract Hydroxymethylenebisphosphonate derivatives have been found to be competitive inhibitors of myo-inositol monophosphatase.