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991.
Adriano Caliman Aliny F. Pires Francisco A. Esteves Reinaldo L. Bozelli Vinicius F. Farjalla 《Biodiversity and Conservation》2010,19(3):651-664
The sub-discipline of biodiversity and ecosystem functioning (BEF) has emerged as a central topic in contemporary ecological
research. However, to date no study has evaluated the prominence and publication biases in BEF research. Herein we report
the results of a careful quantitative assessment of BEF research published in five core general ecology journals from 1990
to 2007 to determine the position of BEF research within ecology, identify patterns of research effort within BEF research,
and discuss their probable proximal and historical causes. The relative importance of BEF publications increased exponentially
during the period analyzed and was significantly greater than the average growth of ecological literature, affirming the prominence
of BEF as a current paradigm in ecology. However, BEF research exhibited a strong bias toward experimental studies on terrestrial
plant communities, with significantly lower effort devoted to the functional aspects of biodiversity in aquatic systems, multiple
trophic level systems, and animal or microbial communities. Such trends may be explained by a combination of methodological
adequacy and historic epistemological differences in ecological thinking. We suggest that BEF researchers should direct more
effort toward the study of aquatic systems and animal communities, emphasize long-term and trophically complex experiments,
such as those with multi-trophic microbial communities, employ larger-scale field observational studies and increase the use
of integrative and theoretical studies. Many technical and analytical methodologies that are already employed in ecological
research, such as stable isotopes, paleobiology, remote sensing, and model selection criteria, can facilitate these aims.
Overcoming the above-mentioned shortcomings of current BEF research will greatly improve our ability to predict how biodiversity
loss will affect ecosystem processes and services in natural ecosystems. 相似文献
992.
Potter A Oldfield V Nunns C Fromont C Ray S Northfield CJ Bryant CJ Scrace SF Robinson D Matossova N Baker L Dokurno P Surgenor AE Davis B Richardson CM Murray JB Moore JD 《Bioorganic & medicinal chemistry letters》2010,20(22):6483-6488
Pin1 is an emerging oncology target strongly implicated in Ras and ErbB2-mediated tumourigenesis. Pin1 isomerizes bonds linking phospho-serine/threonine moieties to proline enabling it to play a key role in proline-directed kinase signalling. Here we report a novel series of Pin1 inhibitors based on a phenyl imidazole acid core that contains sub-μM inhibitors. Compounds have been identified that block prostate cancer cell growth under conditions where Pin1 is essential. 相似文献
993.
Christine E. Brotherton-Pleiss Michael P. Dillon Anthony P.D.W. Ford Joel R. Gever David S. Carter Shelley K. Gleason Clara J. Lin Amy G. Moore Anthony W. Thompson Marzia Villa Yansheng Zhai 《Bioorganic & medicinal chemistry letters》2010,20(3):1031-1036
Despite the extensive literature describing the role of the ATP-gated P2X3 receptors in a variety of physiological processes the potential of antagonists as therapeutic agents has been limited by the lack of drug-like selective molecules. In this paper we report the discovery and optimization of RO-85, a novel drug-like, potent and selective P2X3 antagonist. High-throughput screening of the Roche compound collection identified a small hit series of heterocyclic amides from a large parallel synthesis library. Rapid optimization, facilitated by high-throughput synthesis, focusing on increasing potency and improving drug-likeness resulted in the discovery of RO-85. 相似文献
994.
Laszlo Revesz Achim Schlapbach Reiner Aichholz Janet Dawson Roland Feifel Stuart Hawtin Amanda Littlewood-Evans Guido Koch Markus Kroemer Henrik Möbitz Clemens Scheufler Juraj Velcicky Christine Huppertz 《Bioorganic & medicinal chemistry letters》2010,20(15):4719-4723
Spirocyclopropane- and spiroazetidine-substituted tetracycles 13D–E and 16A are described as orally active MK2 inhibitors. The spiroazetidine derivatives are potent MK2 inhibitors with IC50 <3 nM and inhibit the release of TNFα (IC50<0.3 μM) from hPBMCs and hsp27 phosphorylation in anisomycin stimulated THP-1 cells. The spirocyclopropane analogues are less potent against MK2 (IC50 = 0.05–0.23 μM), less potent in cells (IC50 <1.1 μM), but show good oral absorption. Compound 13E (100 mg/kg po; bid) showed oral activity in rAIA and mCIA, with significant reduction of swelling and histological score. 相似文献
995.
Wu TY Juteau H Ducharme Y Friesen RW Guiral S Dufresne L Poirier H Salem M Riendeau D Mancini J Brideau C 《Bioorganic & medicinal chemistry letters》2010,20(23):6978-6982
Microsomal prostaglandin E(2) synthase (mPGES-1) represents a potential target for novel analgesic and anti-inflammatory agents. High-throughput screening identified several leads of mPGES-1 inhibitors which were further optimized for potency and selectivity. A series of inhibitors bearing a biaryl imidazole scaffold exhibits excellent inhibition of PGE(2) production in enzymatic and cell-based assays. The synthesis of these molecules and their activities will be discussed. 相似文献
996.
Emily M. Stocking Leah Aluisio John R. Atack Pascal Bonaventure Nicholas I. Carruthers Christine Dugovic Anita Everson Ian Fraser Xiaohui Jiang Perry Leung Brian Lord Kiev S. Ly Kirsten L. Morton Diane Nepomuceno Chandravadan R. Shah Jonathan Shelton Akinola Soyode-Johnson Michael A. Letavic 《Bioorganic & medicinal chemistry letters》2010,20(9):2755-2760
Pre-clinical characterization of novel substituted pyrrolidines that are high affinity histamine H3 receptor antagonists is described. These compounds efficiently penetrate the CNS and occupy the histamine H3 receptor in rat brain following oral administration. One compound, (2S,4R)-1-[2-(4-cyclobutyl-[1,4]diazepane-1-carbonyl)-4-(3-fluoro-phenoxy)-pyrrolidin-1-yl]-ethanone, was extensively profiled and shows promise as a potential clinical candidate. 相似文献
997.
Robert R. Singhaus Ronald C. Bernotas Robert Steffan Edward Matelan Elaine Quinet Ponnal Nambi Irene Feingold Christine Huselton Anna Wilhelmsson Annika Goos-Nilsson Jay Wrobel 《Bioorganic & medicinal chemistry letters》2010,20(2):521-525
Replacement of a quinoline with an imidazo[1,2-a]pyridine in a series of liver X receptor (LXR) agonists incorporating a [3-(sulfonyl)aryloxyphenyl] side chain provided high affinity LXR ligands 7. In functional assays of LXR activity, good agonist potency and efficacy were found for several analogs. 相似文献
998.
Kristen L.G. Jones M. Katharine Holloway Hua-Poo Su Steven S. Carroll Christine Burlein Sinoeun Touch Daniel J. DiStefano Rosa I. Sanchez Theresa M. Williams Joseph P. Vacca Craig A. Coburn 《Bioorganic & medicinal chemistry letters》2010,20(14):4065-4068
A series of HIV-1 protease inhibitors containing an epsilon substituted lysinol backbone was synthesized. Two novel synthetic routes using N-boc-l-glutamic acid alpha-benzyl ester and 2,6-diaminopimelic acid were developed. Incorporation of this epsilon substituent enabled access to the S2 pocket of the enzyme, affording high potency inhibitors. Modeling studies and synthetic efforts suggest the potency increase is due to both conformational bias and van der Waals interactions with the S2 pocket. 相似文献
999.
Jeffrey Y. Melamed Amy E. Zartman Nathan R. Kett Anthony L. Gotter Victor N. Uebele Duane R. Reiss Cindra L. Condra Christine Fandozzi Laura S. Lubbers Blake A. Rowe Georgia B. McGaughey Martin Henault Rino Stocco John J. Renger George D. Hartman Mark T. Bilodeau B. Wesley Trotter 《Bioorganic & medicinal chemistry letters》2010,20(15):4700-4703
Administration of Neuropeptide S (NPS) has been shown to produce arousal, that is, independent of novelty and to induce wakefulness by suppressing all stages of sleep, as demonstrated by EEG recordings in rat. Medicinal chemistry efforts have identified a quinolinone class of potent NPSR antagonists that readily cross the blood–brain barrier. We detail here optimization efforts resulting in the identification of a potent NPSR antagonist which dose-dependently and specifically inhibited 125I-NPS binding in the CNS when administered to rats. 相似文献
1000.