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Loughlin WA Pierens GK Petersson MJ Henderson LC Healy PC 《Bioorganic & medicinal chemistry》2008,16(11):6172-6178
The lipophilicity, permeability, solubility, polar surface area and 'rule-of-five' properties were assessed, using QikProp v2.5 (Schr?dinger, Inc.) and ALOGPS 2.1 calculations, for 25 Hyphodermin derivatives. These compounds obeyed the 'rule-of-five', and the calculated physicochemical values were generally within desired limits. All compounds were tested against Glycogen Phosphorylase a (GPa). Four phenyl and benzyl substituted 2-oxo-hexahydro and tetrahydrobenzo[cd]indole carboxylic acids were identified as novel inhibitors of GPa with estimated IC(50) values in the range 0.8-1.3mM. Molecular modelling of these novel inhibitors was used to obtain the main structural features of this class of molecule for future structure-activity relationship studies. 相似文献
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Gayatri Balan Jonathan Bauman Samit Bhattacharya Mayda Castrodad David R. Healy Michael Herr Paul Humphries Sandra Jennings Amit S. Kalgutkar Brendon Kapinos Vishal Khot Kimberly Lazarra Mei Li Yan Li Constantin Neagu Robert Oliver David W. Piotrowski David Price Hong Qi Holly A. Simmons Vishwas M. Paralkar 《Bioorganic & medicinal chemistry letters》2009,19(12):3328-3332
The design and profile of a series of zwitterionic calcium sensing receptor negative allosteric modulators is described. Evaluation of key analogues using a rat model demonstrate a robust response, significantly improved potency over ronacaleret and have the potential as an oral, anabolic treatment for osteoporosis. 相似文献
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N. David Karis Wendy A. Loughlin Ian D. Jenkins Peter C. Healy 《Bioorganic & medicinal chemistry》2009,17(13):4724-4733
Glycogen phosphorylase (GP) plays a crucial role in the conversion of glycogen to glucose-1-phosphate (and in turn glucose) and is a promising target for therapeutic intervention in diabetes. In this study we synthesized new derivatives of 2-oxo-1,2-dihydropyridin-3-yl amides using a facile aminolysis reaction, in which different alkyl and aryl esters and amides are substituted at N-1 and C-3 of the heterocyclic ring. The in vitro inhibitory activity of compounds against glycogen phosphorylase was evaluated. From this series the most potent compound exhibits good GPa inhibition (IC50 = 6.3 μM). A preliminary study of these compounds showed that anti-GP activity was decreased by the incorporation of a C3–N carbonyl group and favored by increased lipophilicity. 相似文献
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A. Heenan S. D. Simpson M. G. Meekan S. D. Healy V. A. Braithwaite 《Journal of fish biology》2009,75(7):1857-1867
To determine whether enhancing the survival of new recruits is a sensible target for the restorative management of depleted coral‐reef fish populations, settlement‐stage ambon damsel fish Pomacentrus amboinensis were captured, tagged and then either released immediately onto small artificial reefs or held in aquaria for 1 week prior to release. Holding conditions were varied to determine whether they affected survival of fish: half the fish were held in bare tanks (non‐enriched) and the other half in tanks containing coral and sand (enriched). Holding fish for this short period had a significantly positive effect on survivorship relative to the settlement‐stage treatment group that were released immediately. The enrichment of holding conditions made no appreciable difference on the survival of fish once released onto the reef. It did, however, have a positive effect on the survival of fish while in captivity, thus supporting the case for the provision of simple environmental enrichment in fish husbandry. Collecting and holding settlement‐stage fish for at least a week before release appear to increase the short‐term survival of released fish; whether it is an effective method for longer‐term enhancement of locally depleted coral‐reef fish populations will require further study. 相似文献
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Men and women differ in their ability to solve spatial problems. There are two possible proximate explanations for this: (i) men and women differ in the kind (and value) of information they use and/or (ii) their cognitive abilities differ with respect to spatial problems. Using a simple computerized task which could be solved either by choosing an object based on what it looked like, or by its location, we found that the women relied on the object's visual features to solve the task, while the men used both visual and location information. There were no differences between the sexes in memory for the visual features of the objects, but women were poorer than men at remembering the locations of objects. 相似文献
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Capsule: Hooded Crows Corvus cornix selected nesting trees based on species, height, grouping and distance from an occupied house. Nest re-use was common and pairs that re-used old nests produced more fledglings than those that built a new nest.Aims: To determine the features of trees that influenced whether they were used by Hooded Crows as nest sites, to establish what factors influenced nest re-use between years and to explore potential costs or benefits of nest re-use.Methods: In a large area of Orkney, Scotland, the features of trees that contained a Hooded Crow nest were compared to those of trees where nests were absent. Patterns of nest re-use between years were examined in relation to the availability of alternative sites, previous nesting success and the number of equivalent options to the tree used previously within 200?m of this site.Results: Hooded Crows favoured spruce and pine trees as nest sites, above the most locally abundant tree species, elder and willow. Preference for trees increased with tree height, local tree density and distance from occupied houses. Over half of the crows studied re-used an old nest when one was available and crows that re-used an old nest fledged more offspring than those that built a new nest. The likelihood of a new nest being built increased as the number of potential locations to build increased. Territories where a nest survived the winter were more likely to be reoccupied the following year than those where nests fell, while territories with fewer trees around the old site were most likely to be abandoned, suggesting that those were territories of lower quality.Conclusions: Hooded Crows displayed strong preferences for nest sites that might favour nesting success by offering concealment, shelter and protection from ground-based predators. Nest re-use was common, especially when alternative sites were scarce, and appeared to facilitate greater reproductive output. 相似文献