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101.
102.
Effects of exercise in the cold on blood clotting and platelets 总被引:1,自引:0,他引:1
103.
The mechanism of ferrous ion binding to prolyl hydroxylase (prolyl-glycyl-peptide,2-oxoglutarate:oxygen oxidoreductase, EC 1.14.11.2) was studied according to Koshland's curve-fitting procedure (Cornish-Bowden, A. and Koshland, Jr., D.E. (1970) Biochemistry 9, 3325--3336). The calculated data obtained by means of the unrestricted Adair equation were found to provide an adequate fit with experimentally obtained values, whereas those obtained on the basis of Michaelis-Menten kinetics did not. This suggests that prolyl hydroxylase could be an allosteric enzyme under positive heterotropic control. 相似文献
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Immunochemical characterization of the cell surface carbohydrate antigens of Peptostreptococcus anaerobius 总被引:1,自引:0,他引:1
Two carbohydrate antigens were isolated from the cell surface of Peptostreptococcus anaerobius. One, extracted from purified cell walls with NaOH, contained glucose and phosphorus, with traces of galactosamine and glucosamine. Serological activity was detected by a 'dot blot' procedure. The second antigen, extracted from cell membranes with phenol and purified by chromatography on Sepharose 6B and an immunoadsorbent column, contained glucose, glycerol phosphate, phosphorus and fatty acids. Antigenicity of this extract could also be demonstrated by an ELISA technique. 相似文献
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Cumming JG Tucker H Oldfield J Fielding C Highton A Faull A Wild M Brown D Wells S Shaw J 《Bioorganic & medicinal chemistry letters》2012,22(4):1655-1659
Modifications to a series of potent and selective substituted 1-(3,3-diphenylpropyl)-piperidine phenylacetamide CCR5 antagonists were explored with the aim of reducing affinity at the hERG cardiac ion channel. Replacement of one aromatic ring in the diphenylpropyl region with less lipophilic, saturated heterocyclic rings and subsequent optimisation of the other phenyl ring led to the identification of clinical compound AZD5672 which retained excellent potency while reducing hERG affinity. Modulating lipophilicity affected the interplay between potency, hERG affinity and absorption. AZD5672 was found to have an acceptable balance of these properties and was progressed to a phase II clinical trial to test the hypothesis that inhibition of CCR5 will bring benefits in the treatment of rheumatoid arthritis. 相似文献
109.
Cumming JN Smith EM Wang L Misiaszek J Durkin J Pan J Iserloh U Wu Y Zhu Z Strickland C Voigt J Chen X Kennedy ME Kuvelkar R Hyde LA Cox K Favreau L Czarniecki MF Greenlee WJ McKittrick BA Parker EM Stamford AW 《Bioorganic & medicinal chemistry letters》2012,22(7):2444-2449
From an initial lead 1, a structure-based design approach led to identification of a novel, high-affinity iminohydantoin BACE1 inhibitor that lowers CNS-derived Aβ following oral administration to rats. Herein we report SAR development in the S3 and F' subsites of BACE1 for this series, the synthetic approaches employed in this effort, and in vivo data for the optimized compound. 相似文献
110.
Cumming JG Brown SJ Cooper AE Faull AW Flynn AP Grime K Oldfield J Shaw JS Shepherd E Tucker H Whittaker D 《Bioorganic & medicinal chemistry letters》2006,16(13):3533-3536
SAR and PK studies led to the identification of N-(1-{(3R)-3-(3,5-difluorophenyl)-3-[4-methanesulfonylphenyl] propyl}piperidin-4-yl)-N-ethyl-2-[4-methanesulfonylphenyl]acetamide as a highly potent and selective ligand for the human CCR5 chemokine receptor with good oral pharmacokinetic properties. 相似文献