James E. J. Mills

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1. Lung irritant receptors have been studied in rabbits by recording action potentials from single vagal nerve fibres. Some of the rabbits were bilaterally vagotomized, and some paralysed and artificially ventilated.2. The receptors gave rapidly adapting irregular discharges on inflation and deflation of the lungs. Many were stimulated by insufflation of(More)
An extensive crystal survey of the Cambridge Structural Database has been carried out to provide hydrogen-bond data for use in drug-design strategies. Previous crystal surveys have generated 1D frequency distributions of hydrogen-bond distances and angles, which are not sufficient to model the hydrogen bond as a ligand-receptor interaction. For each(More)
Inhibition of N-myristoyltransferase has been validated pre-clinically as a target for the treatment of fungal and trypanosome infections, using species-specific inhibitors. In order to identify inhibitors of protozoan NMTs, we chose to screen a diverse subset of the Pfizer corporate collection against Plasmodium falciparum and Leishmania donovani NMTs.(More)
Succinyl hydroxamates 1 and 2 are disclosed as novel series of potent and selective inhibitors of procollagen C-proteinase (PCP) which may have potential as anti-fibrotic agents. Carboxamide 7 demonstrated good PCP inhibition and had excellent selectivity over MMPs involved in wound healing. In addition, 7 was effective in a cell-based model of collagen(More)
1. The effects of vagotomy on the respiratory responses of guinea-pigs to anaphylactic reactions and to intravenous injections of histamine acid phosphate are described.2. In spontaneously breathing guinea-pigs, vagotomy reduced by 50% or more the decreases in total lung conductance (bronchoconstriction) and the decreases in lung compliance, and almost(More)
A new computational algorithm for protein binding sites characterization and comparison has been developed, which uses a common reference framework of the projected ligand-space four-point pharmacophore fingerprints, includes cavity shape, and can be used with diverse proteins as no structural alignment is required. Protein binding sites are first described(More)
4-(Diphenylmethyl)-1-piperidinemethanimine (1) is a potent oral gastric antisecretory agent in rats but contains a strong anticholinergic component. Since a nonanticholinergic gastric antisecretory drug would be useful in the treatment of peptic ulcer disease, a program was initiated by us to find such an agent based on 1. Compound 1 contains structural(More)
The postprocessing of high-throughput screening (HTS) results is complicated by the occurrence of false positives (inactive compounds misidentified as active by the primary screen) and false negatives (active compounds misidentified as inactive by the primary screen). An activity cutoff is frequently used to select "active" compounds from HTS data; however,(More)