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排序方式: 共有176条查询结果,搜索用时 15 毫秒
71.
Lee M Dukat M Liao L Flammia D Damaj MI Martin B Glennon RA 《Bioorganic & medicinal chemistry letters》2002,12(15):1989-1992
A total of 24 aryl-substituted analogues of nicotine (1a) and two related series of nicotinic ligands, aminomethylpyridines 3 and ether analogues 8, were examined to determine if they bind at alpha4beta2 nACh receptors in a common manner. A modest correlation (r=0.785) was found between the affinities of the nicotine analogues and derivatives of 3, but little correlation (r=0.348) was found with analogues 8. However, a modest correlation (r=0.742) exists between the binding of analogues 3 and 8. It seems that 1-series and 8-series compounds bind differently but that the 3-series compounds share some intermediate binding similarity with both. 相似文献
72.
Richland Tester Xuefei Tan Gregory R. Luedtke Imad Nashashibi Kurt Schinzel Weiling Liang Joon Jung Sundeep Dugar Albert Liclican Jocelyn Tabora Daniel E. Levy Steven Do 《Bioorganic & medicinal chemistry letters》2010,20(8):2560-2563
Optimization of a tri-substituted N-pyridyl amide led to the discovery of a new class of potent N-pyrimidyl amide based p38α MAP kinase inhibitors. Initial SAR studies led to the identification of 5-dihydrofuran as an optimal hydrophobic group. Additional side chain modifications resulted in the introduction of hydrogen bond interactions. Through extensive SAR studies, analogs bearing free amino groups and alternatives to the parent (S)-α-methyl benzyl moiety were identified. These compounds exhibited improved cellular activities and maintained balance between p38α and CYP3A4 inhibition. 相似文献
73.
Amide-based inhibitors of p38α MAP kinase. Part 1: Discovery of novel N-pyridyl amide lead molecules
Gregory R. Luedtke Kurt Schinzel Xuefei Tan Richland W. Tester Imad Nashashibi Yong-jin Xu Sundeep Dugar Daniel E. Levy Joon Jung 《Bioorganic & medicinal chemistry letters》2010,20(8):2556-2559
A novel series of N-pyridyl amides as potent p38α kinase inhibitors is described. Based on the structural similarities between the initial hit and a well-known imidazole pyrimidine series of p38α inhibitors, potencies within the newly discovered series were quickly improved by installation of an (S)-α-methylbenzyl moiety at the 2-position of the pyridine ring. The proposed binding modes of the new series to p38α were evaluated against SAR findings and provided rationale for further development of this series of molecules. 相似文献
74.
Imad M. Tleyjeh Aref A. Bin. Abdulhak Muhammad Riaz Musa A. Garbati Mohamad Al-Tannir Faisal A. Alasmari Mushabab AlGhamdi Abdur Rahman Khan Patricia J. Erwin Alex J. Sutton Larry M. Baddour 《PloS one》2013,8(3)
Background
Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI.Purpose
We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI.Data source
We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI.Study selection
Two authors independently reviewed the studies for eligibility.Data extraction
Data about studies characteristics, adjusted effect estimates and quality were extracted.Data synthesis
Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097).Conclusion
In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics. 相似文献75.
Rafael Hernández-de-Diego Noemi Boix-Chova David Gómez-Cabrero Jesper Tegner Imad Abugessaisa Ana Conesa 《BMC systems biology》2014,8(Z2):S9
High-throughput sequencing assays are now routinely used to study different aspects of genome organization. As decreasing costs and widespread availability of sequencing enable more laboratories to use sequencing assays in their research projects, the number of samples and replicates in these experiments can quickly grow to several dozens of samples and thus require standardized annotation, storage and management of preprocessing steps. As a part of the STATegra project, we have developed an Experiment Management System (EMS) for high throughput omics data that supports different types of sequencing-based assays such as RNA-seq, ChIP-seq, Methyl-seq, etc, as well as proteomics and metabolomics data. The STATegra EMS provides metadata annotation of experimental design, samples and processing pipelines, as well as storage of different types of data files, from raw data to ready-to-use measurements. The system has been developed to provide research laboratories with a freely-available, integrated system that offers a simple and effective way for experiment annotation and tracking of analysis procedures. 相似文献
76.
Simsek R Chang-Fong J Lee M Dukat M Imad Damaj M Martin BR Glennon RA 《Bioorganic & medicinal chemistry letters》2003,13(17):2917-2920
Quaternization via N-methylation of the terminal amines of a series of 3-(dialkylaminoethoxy)pyridines resulted in analogues that displayed up to 50-60-fold enhanced affinity for nicotinic acetylcholinergic (nACh) receptors. Several of these compounds displayed antinociceptive properties in mice using the tail-flick assay and serve as possible leads for the development of novel analgesic agents. 相似文献
77.
De novo genome sequencing and comparative genomics of date palm (Phoenix dactylifera) 总被引:1,自引:0,他引:1
Al-Dous EK George B Al-Mahmoud ME Al-Jaber MY Wang H Salameh YM Al-Azwani EK Chaluvadi S Pontaroli AC DeBarry J Arondel V Ohlrogge J Saie IJ Suliman-Elmeer KM Bennetzen JL Kruegger RR Malek JA 《Nature biotechnology》2011,29(6):521-527
Date palm is one of the most economically important woody crops cultivated in the Middle East and North Africa and is a good candidate for improving agricultural yields in arid environments. Nonetheless, long generation times (5-8 years) and dioecy (separate male and female trees) have complicated its cultivation and genetic analysis. To address these issues, we assembled a draft genome for a Khalas variety female date palm, the first publicly available resource of its type for a member of the order Arecales. The ~380 Mb sequence, spanning mainly gene-rich regions, includes >25,000 gene models and is predicted to cover ~90% of genes and ~60% of the genome. Sequencing of eight other cultivars, including females of the Deglet Noor and Medjool varieties and their backcrossed males, identified >3.5 million polymorphic sites, including >10,000 genic copy number variations. A small subset of these polymorphisms can distinguish multiple varieties. We identified a region of the genome linked to gender and found evidence that date palm employs an XY system of gender inheritance. 相似文献
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