Toby J. Underwood

TEMPO‐Mediated Electrooxidation of Primary and Secondary Alcohols in a Microfluidic Electrolytic Cell

A general procedure for the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated electrooxidation of primary and secondary alcohols modified for application in a microfluidic electrolytic cell is described. The electrocatalytic system utilises a buffered aqueous tert-butanol reaction medium, which operates effectively without the requirement for additional electrolyte, providing a mild protocol for the oxidation of alcohols to aldehydes and ketones at ambient temperature on a laboratory scale. Optimisation of the process is discussed along with the oxidation of 15 representative alcohols.

Discovery of PF-184563, a potent and selective V1a antagonist for the treatment of dysmenorrhoea. The influence of compound flexibility on microsomal stability

The V1a receptor has emerged as an attractive target for a range of indications including Raynauds disease and dysmenorrhoea. As part of an effort to discover a new class of orally active V1a antagonist, we optimised a highly lipophilic, metabolically unstable lead into a range of potent, selective and metabolically stable V1a antagonists. In this communication, we demonstrate the series-dependent effect of limiting the number of rotatable bonds in order to decrease Cytochrome P450-mediated metabolism. This effort culminated in the discovery of PF-184563, a novel, selective V1a antagonist with excellent in vitro and in vivo properties.