William L. Mitchell

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Selective CB2 receptor agonists are promising potential therapeutic agents for the treatment of inflammatory and neuropathic pain. A focused screen identified a pyrimidine ester as a partial agonist at the CB2 receptor with micromolar potency. Subsequent lead optimization identified 35, GW842166X, as the optimal compound in the series. 35 has an oral ED50(More)
The need for a real-world driving problem to guide technology development has long been recognised. However, this does not guarantee the identification of requirements for technology development. This paper argues that a more systematic approach is needed for choosing and making best use of a driving problem for CVE technology. The method consists of(More)
The title binaphthyls 19 and 26, which are the positional isomers of 2-methoxy-2'-(diphenylphosphino)-1,1'-binaphthyl (MOP, 19) and 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN, 26), have been synthesized by Suzuki coupling as the key step (10 + 15-->18), followed by functional group transformations, involving C-P and C-N bond formation (18-->19 and 18-->23).(More)
This paper reports on the elicitation of requirements for Virtual Actors in Collaborative Virtual Learning Environments (CVLEs). The methodological approach followed involves the phased development of a series of learning environments which are observed in use by parents, children and teachers. The focus of study is on the interactivity and social(More)
Daphne Economou , William L. Mitchell and Steve R. Pettifer 1Sony Broadcast and Professional Research Labs, Jays Close, Basingstoke, RG22 4SB, England, Email: Daphne.Economou@adv.sonybpe.com 2Education and Training Group, The British Council Bridgewater House, 58 Whitworth Street, Manchester, M1 6BB, England, E-mail: William.Mitchell@britishcouncil.org(More)
SAR of a novel series of pyridazine-derived γ-secretase modulators is described. Compound 25 was found to be a potent modulator in vitro, which on further profiling, was found to decrease Aβ42 and Aβ40, and maintain the levels of total Aβ. Furthermore, 25 demonstrated excellent pharmacokinetic parameters as well as good CNS penetration in the rat.
We report on the development of a series of pyrimidine carboxylic acids that are potent and selective inhibitors of kynurenine monooxygenase and competitive for kynurenine. We describe the SAR for this novel series and report on their inhibition of KMO activity in biochemical and cellular assays and their selectivity against other kynurenine pathway(More)
SAR of a novel series of pyridine-derived γ-secretase modulators is described. Compound 5 was found to be a potent modulator in vitro, which on further profiling, was found to decrease Aβ42 and Aβ40, and maintain (or increase) the levels of total Aβ. Furthermore, representative compounds 1 and 5 demonstrated in vivo efficacy to lower Aβ42 in the brain(More)
MAVERIK [I] and Deva [S] are VE systems under development in the Advanced Interfaces Group at the University of Manchester. Previous experience highlighted the need for a different approach to spatial management and rendering in VEs (MAVERIK) as well as for techniques and tools for describing, managing and distributing behaviour in shared environments(More)
This paper argues that the development of virtual actor technology must be guided by application and end user needs. Two objectives drive the development of the '<i>Senet</i>' project described in this paper: to develop a set of design guidelines for the use of virtual actors in Collaborative Virtual Environments (CVEs) for learning, and to inform the(More)