Richard Bell

GR159897 and related analogues as highly potent, orally active non-peptide neurokinin NK2 receptor antagonists.

Abstract Optimisation of NK 2 receptor affinity in a series of sulfur derivatives resulted in the identification of Highly potent 5-fluoroindol-3-ylethyl[4-(phenylsulfinyl methyl])piperidines. Further structure activity analysis led to GR 159897 an NK 2 receptor antagonist which potently blocks agonist-induced bronchoconstriction in the guinea-pig when administered by peripheral and oral routes.

The squalestatins : potent inhibitors of squalene synthase : the role of the tricarboxylic acid moiety

In squalestatins possessing at C6 either a 4,6-dimethyloctenoate ester or a hydroxyl group, the 5-carboxylic acid is crucial for squalene synthase inhibitory activity. In the former seires, free carboxylic acids are not required at C3 or C4 for potent enzyme inhibitory activity whereas in the latter series esterification of the carboxylic acids at C3 or C4 results in a significant reduction in enzyme inhibitory activity.

Semi-synthetic qualestatins: Squalene synthase inhibition and antifungal activity. The SAR of C6 and C7 modifications

Abstract We describe herein a protection/deprotection strategy that enables efficient transformation of natural Squalestatin S1 into C6 and C7 acyl analogues. We present the mammalian and fungal SQS enzyme activity and whole cell antifungal activity of the semi-synthetic Squalestatins.