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101.
Bioisosteric approach to the discovery of imidazo[1,2-a]pyrazines as potent Aurora kinase inhibitors
Meng Z Kulkarni BA Kerekes AD Mandal AK Esposite SJ Belanger DB Reddy PA Basso AD Tevar S Gray K Jones J Smith EB Doll RJ Siddiqui MA 《Bioorganic & medicinal chemistry letters》2011,21(1):592-598
Our continued effort toward the development of the imidazo[1,2-a]pyrazine scaffold as Aurora kinase inhibitors is described. Bioisosteric approach was applied to optimize the 8-position of the core. Several new potent Aurora A/B dual inhibitors, such as 25k and 25l, were identified. 相似文献
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The combination of polyacrylamide gel electrophoresis and Concanavalin-A-Sepharose affinity chromatography has permitted the isolation on a preparative scale, of four molecular forms of rat alpha1-fetoprotein: a "slow" and a "fast" fraction, each separable into Concanavalin-A-adorbed ("high carbohydrate", i.e. rich in accessible alphaD-Mannosyl and alphaD-Glucosyl residues) and a Concanavalin-A-non adsorbed ("low carbohydrate") fractions. These four iso-alpha-fetoproteins (iso-AFP) bind estradiol-17beta. However, they disclose differences in both their association constants and number of binding sites for this hormone. Very high affinity sites (10(9)) are mainly located on the "slow-low carbohydrate" form. Low affinity, high capacity sites are preferentially located on the "high carbohydrate" form. These results confirm the molecular and functional heterogeneity of rat AFP and suggest that the carbohydrate moiety of the protein may have a role in estrogen-AFP interactions. 相似文献
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Inoculation with Fusarium udum Butl. produced more wilt of pigeon-pea in sterilized than in unsterilized soils at the same pH. From unsterilized soils with low disease incidence, nine fungi, Bacillus subtilis and an Actinomyces were isolated. The number of isolations of a particular organism varied from month to month during the cropping season of pigeon-pea in Delhi. Interaction of Fusarium udum and other organisms isolated was studied. Aspergillus niger and A. terreus secreted inhibitory substances in potato-dextrose broth: Bacillus subtilis inhibited growth on solid medium and also produced a toxic substance in potato-dextrose broth. The nature of the medium employed and period of growth were important factors in the production of the inhibitory principle, which is thermostable. The low incidence of pigeon-pea wilt in unsterilized soils may result from the inhibitory activity of the associated microflora in the soil. 相似文献