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GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor.
The discovery and characterization of 2-arylmethyloxy-5-subtitutent-N-arylbenzamides with potent LRRK2 activities exemplified by GSK2578215A which exhibits biochemical IC(50)s of around 10 nM against both wild-type L RRK2 and the G2019S mutant. Expand
Structure-activity relationships of antifilarial antimycin analogues: a multivariate pattern recognition study.
Analysis of the structure-activity relationships of a series of novel antifilarial antimycin A1 analogues indicated that membrane or lipid solubility is an important determinant in biological activity agreeing with the proposed primary mode of action of the compounds as disrupters of cuticular glucose uptake. Expand
Discovery of novel, non-acidic 1,5-biaryl pyrrole EP1 receptor antagonists.
Replacement of the carboxylic acid group in a series of previously described 1,5-biaryl pyrrole EP1 receptor antagonists led to the discovery of various novel non-acidic antagonists. SeveralExpand
Isosteres of the DNA polymerase inhibitor aphidicolin as potential antiviral agents against human herpes viruses.
A variety of isosteres of the DNA polymerase inhibitor aphidicolin were synthesized as potential antiherpes agents and the 4aS isomer 36 was shown to account for the observed antiviral activity noted against herpes simplex virus 1 and human cytomegalovirus. Expand
Discovery of 4-[3-(trans-3-dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin-2-one (4991W93), a 5HT(1B/1D) receptor partial agonist and a potent inhibitor of electrically induced plasma
4-[3-(trans-3-Dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin-2-one (4991W93, 1) was identified as a partial agonist against 5HT(1B/1D) receptors, with low intrinsic activity. Expand
Pyridine-3-carboxamides as novel CB(2) agonists for analgesia.
The medicinal chemistry approach which led to the discovery of a novel pyridine-3-carboxamide series of CB(2) receptor agonists was described and the identification of analogue 14a which demonstrated efficacy in an in vivo model of inflammatory pain. Expand
GSK 2578215 A ; A potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK 2 kinase inhibitor
Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for some forms of Parkinson’s disease. Here we report the discovery and characterization ofExpand
Discovery of 5-substituent-N-arylbenzamide derivatives as potent, selective and orally bioavailable LRRK2 inhibitors.
The discovery of 5-substituent-N-arylbenzamide derivatives as novel LRRK2 inhibitors is reported, which demonstrated potent L RRK2 inhibition activity, high selectivity across the kinome, good brain exposure, and high oral bioavailability. Expand
Pyrazolopyridazine alpha-2-delta-1 ligands for the treatment of neuropathic pain.
Optimization of the novel alpha-2-delta-1 ligand 4 provided compounds 37 and 38 which have improved DMPK profiles, good in vivo analgesic activity and in vitro selectivity over alpha-2-delta-2. AnExpand
Synthesis and biological evaluation of the L-enantiomer of 2'-deoxy-5-ethyl-4'-thiouridine
Racemic 2'-deoxy-5-ethyl-4'-thiouridine was synthesised utilising the stereoselective iodolactonisation of 3-(tert-butyldimethyIsilyl)oxy-N,N-dimethyl-4-pentenamide as the key transformation. TheExpand