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排序方式: 共有251条查询结果,搜索用时 453 毫秒
131.
Jason E. Imbriglio Sookhee Chang Rui Liang Subharekha Raghavan Darby Schmidt Abby Smenton Scott Tria Thomas O. Schrader Jae-Kyu Jung Craig Esser Tom G. Holt Michael S. Wolff Andrew K.P. Taggart Kang Cheng Ester Carballo-Jane M. Gerard Waters James R. Tata Steven L. Colletti 《Bioorganic & medicinal chemistry letters》2010,20(15):4472-4474
5-Alkyl and aryl-pyrazole-acids have been identified as a new class of selective, small-molecule, agonists of the human orphan G-protein-coupled receptor GPR109a, a high affinity receptor for the HDL-raising drug nicotinic acid. 相似文献
132.
BackgroundInjury is a significant cause of childhood death and can result in substantial long-term disability. Injuries are more common in children from socio-economically deprived families, contributing to health inequalities between the most and least affluent. However, little is known about how the relationship between injuries and deprivation has changed over time in the UK.MethodsWe conducted a cohort study of all children under 5 registered in one of 495 UK general practices that contributed medical data to The Health Improvement Network database between 1990–2009. We estimated the incidence of fractures, burns and poisonings by age, sex, socio-economic group and calendar period and adjusted incidence rate ratios (IRR) comparing the least and most socio-economically deprived areas over time. Estimates of the UK annual burden of injuries and the excess burden attributable to deprivation were derived from incidence rates.ResultsThe cohort of 979,383 children experienced 20,804 fractures, 15,880 burns and 10,155 poisonings, equating to an incidence of 75.8/10,000 person-years (95% confidence interval 74.8–76.9) for fractures, 57.9 (57.0–58.9) for burns and 37.3 (35.6–38.0) for poisonings. Incidence rates decreased over time for burns and poisonings and increased for fractures (p<0.001 test for trend for each injury). They were significantly higher in more deprived households (IRR test for trend p<0.001 for each injury type) and these gradients persisted over time. We estimate that 865 fractures, 3,763 burns and 3,043 poisonings could be prevented each year in the UK if incidence rates could be reduced to those of the most affluent areas.ConclusionsThe incidence of burns and poisonings declined between 1990 and 2009 but increased for fractures. Despite these changes, strong socio-economic inequalities persisted resulting in an estimated 9,000 additional medically-attended injuries per year in under-5s. 相似文献
133.
Duffy JL Rano TA Kevin NJ Chapman KT Schleif WA Olsen DB Stahlhut M Rutkowski CA Kuo LC Jin L Lin JH Emini EA Tata JR 《Bioorganic & medicinal chemistry letters》2003,13(15):2569-2572
A biaryl pyridylfuran P(3) substituent on the hydroxyethylene isostere scaffold affords HIV protease inhibitors (PI's) with picomolar (IC(50)) potency against the protease enzymes from PI-resistant HIV-1 strains. Inclusion of a gem-dimethyl substituent afforded compound 3 with 100% oral bioavailability (dogs) and more than double the t(1/2) of indinavir. Inhibition of multiple P450 isoforms is dependent on the regiochemistry of the pyridyl nitrogen in these compounds. 相似文献
134.
M.S. Mary Mangaiyarkarasi S. Vincent S. Janarthanan T. Subba Rao B.V.R. Tata 《Saudi Journal of Biological Sciences》2011,18(2):157-167
Detoxification of Cr(VI) under alkaline pH requires attention due to the alkaline nature of many effluents. An alkaliphilic gram-positive Bacillus subtilis isolated from tannery effluent contaminated soil was found to grow and reduce Cr(VI) up to 100% at an alkaline pH 9. Decrease in pH to acidic range with growth of the bacterium signified the role played by metabolites (organic acids) in chromium resistance and reduction mechanism. The XPS and FT-IR spectra confirmed the reduction of Cr(VI) by bacteria into +3 oxidation state. Chromate reductase assay indicated that the reduction was mediated by constitutive membrane bound enzymes. The kinetics of Cr(VI) reduction activity derived using the monod equation proved (Ks = 0.00032) high affinity of the organism to the metal. This study thus helped to localize the reduction activity at subcellular level in a chromium resistant alkaliphilic Bacillus sp. 相似文献
135.
Graham TH Shen HC Liu W Xiong Y Verras A Bleasby K Bhatt UR Chabin RM Chen D Chen Q Garcia-Calvo M Geissler WM He H Lassman ME Shen Z Tong X Tung EC Xie D Xu S Colletti SL Tata JR Hale JJ Pinto S Shen DM 《Bioorganic & medicinal chemistry letters》2012,22(1):658-665
Novel prolylcarboxypeptidase (PrCP) inhibitors with nanomolar IC(50) values were prepared by replacing the previously described dichlorobenzimidazole-substituted pyrrolidine amides with a variety of substituted benzylamine amides. In contrast to prior series, the compounds demonstrated minimal inhibition shift in whole serum and minimal recognition by P-glycoprotein (P-gp) efflux transporters. The compounds were also cell permeable and demonstrated in vivo brain exposure. The in vivo effect of compound (S)-6e on weight loss in an established diet-induced obesity (eDIO) mouse model was studied. 相似文献
136.
Wu Z Yang C Graham TH Verras A Chabin RM Xu S Tong X Xie D Lassman ME Bhatt UR Garcia-Calvo MM Shen Z Chen Q Bleasby K Sinharoy R Hale JJ Tata JR Pinto S Colletti SL Shen DM 《Bioorganic & medicinal chemistry letters》2012,22(4):1727-1730
Efforts were dedicated to develop potent and brain penetrant prolylcarboxypeptidase (PrCP) inhibitors by replacing the amide group of original leads 1 and 2 with heterocycles. Aminopyrimidines including compound 32a were identified to display good PrCP inhibitory activity (32a, IC(50)=43 nM) and impressive ability to penetrate brain in mice (brain/plasma ratio: 1.4). 相似文献
137.
A procedure for the isolation of enzymically active rat-liver nuclei 总被引:67,自引:44,他引:23
138.
An assessment of Motorola CodeLink™ microarray performance for gene expression profiling applications
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139.
Scott B. Hoyt Jerry Taylor Clare London Amjad Ali Feroze Ujjainwalla Jim Tata Mary Struthers Doris Cully Tom Wisniewski Ning Ren Charlene Bopp Andrea Sok Andreas Verras Daniel McMasters Qing Chen Elaine Tung Wei Tang Gino Salituro Yusheng Xiong 《Bioorganic & medicinal chemistry letters》2017,27(11):2384-2388
We report the discovery and hit-to-lead optimization of a structurally novel indazole series of CYP11B2 inhibitors. Benchmark compound 34 from this series displays potent inhibition of CYP11B2, high selectivity versus related steroidal and hepatic CYP targets, and lead-like physical and pharmacokinetic properties. On the basis of these and other data, the indazole series was progressed to lead optimization for further refinement. 相似文献
140.
Kim RM Chang J Lins AR Brady E Candelore MR Dallas-Yang Q Ding V Dragovic J Iliff S Jiang G Mock S Qureshi S Saperstein R Szalkowski D Tamvakopoulos C Tota L Wright M Yang X Tata JR Chapman K Zhang BB Parmee ER 《Bioorganic & medicinal chemistry letters》2008,18(13):3701-3705
The discovery and optimization of potent and selective aminobenzimidazole glucagon receptor antagonists are described. One compound possessing moderate pharmacokinetic properties in multiple preclinical species was orally efficacious at inhibiting glucagon-mediated glucose excursion in transgenic mice expressing the human glucagon receptor, and in rhesus monkeys. The compound also significantly lowered glucose levels in a murine model of diabetes. 相似文献