Jeremy John Payne

4-Phenyl-7-azaindoles as potent and selective IKK2 inhibitors

The synthesis and SAR of a novel series of IKK2 inhibitors are described. Modification around the hinge binding region of the 7-azaindole led to a series of potent and selective inhibitors with good cellular activity.

Identification of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidinyl] amines and ethers as potent and selective cyclooxygenase-2 inhibitors.

A novel series of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidine-based cyclooxygenase-2 (COX-2) inhibitors, which have a different arrangement of substituents compared to the more common 1,2-diarylheterocycle based molecules, have been discovered. For example, 2-(butyloxy)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)pyrimidine (47), a member of the 2-pyrimidinyl ether series, has been shown to be a potent and selective inhibitor with a favourable pharmacokinetic profile, high brain penetration and good efficacy in rat models of hypersensitivity.

4-Phenyl-7-Azaindoles as Potent, Selective and Bioavailable Ikk2 Inhibitors Demonstrating Good in Vivo Efficacy.

The lead optimization of a series of potent azaindole IKK2 inhibitors is described. Optimization of the human whole blood activity and selectivity over IKK1 in parallel led to the discovery of 16, a potent and selective IKK2 inhibitor showing good efficacy in a rat model of neutrophil activation.

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.