(β-D-ribofuranosyl)formamidine in the design and synthesis of 2-(β-D-ribofuranosyl)pyrimidines, including RF-containing derivatives

A wide range of novel 2-(β-D-ribofuranosyl)pyrimidines, including RF-containing derivatives, have been synthesized by the reaction of (β-D-ribofuranosyl)formamidine with various dielectrophilic substrates such as 3-alkoxy- and 3-chloro-1-(polyfluoroalkyl)propen-1-ones, 3-nitro- and 3-(phenylethynyl)chromones and heteroaryl acetylenic ketones. Polyfluoroalkyl-containing 2-(β-D-ribofuranosyl)pyrimidine derivatives have been synthesized by the reaction of (β-D-ribofuranosyl)formamidine with dielectrophilic substrates such as 3-alkoxy- and 3-chloro-1-(polyfluoroalkyl) propen-1-ones, 3-nitro- and 3-(phenylethynyl)chromones and heteroaryl acetylenic ketones. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

In Silico Prediction of Estrogen Receptor Subtype Binding Affinity and Selectivity Using Statistical Methods and Molecular Docking with 2-Arylnaphthalenes and 2-Arylquinolines

Over the years development of selective estrogen receptor (ER) ligands has been of great concern to researchers involved in the chemistry and pharmacology of anticancer drugs, resulting in numerous synthesized selective ER subtype inhibitors. In this work, a data set of 82 ER ligands with ERα and ERβ inhibitory activities was built, and quantitative structure-activity relationship (QSAR) methods based on the two linear (multiple linear regression, MLR, partial least squares regression, PLSR) and a nonlinear statistical method (Bayesian regularized neural network, BRNN) were applied to investigate the potential relationship of molecular structural features related to the activity and selectivity of these ligands. For ERα and ERβ, the performances of the MLR and PLSR models are superior to the BRNN model, giving more reasonable statistical properties (ERα: for MLR, Rtr2 = 0.72, Qte2 = 0.63; for PLSR, Rtr2 = 0.92, Qte2 = 0.84. ERβ: for MLR, Rtr2 = 0.75, Qte2 = 0.75; for PLSR, Rtr2 = 0.98, Qte2 = 0.80). The MLR method is also more powerful than other two methods for generating the subtype selectivity models, resulting in Rtr2 = 0.74 and Qte2 = 0.80. In addition, the molecular docking method was also used to explore the possible binding modes of the ligands and a relationship between the 3D-binding modes and the 2D-molecular structural features of ligands was further explored. The results show that the binding affinity strength for both ERα and ERβ is more correlated with the atom fragment type, polarity, electronegativites and hydrophobicity. The substitutent in position 8 of the naphthalene or the quinoline plane and the space orientation of these two planes contribute the most to the subtype selectivity on the basis of similar hydrogen bond interactions between binding ligands and both ER subtypes. The QSAR models built together with the docking procedure should be of great advantage for screening and designing ER ligands with improved affinity and subtype selectivity property

‘Orientalism is a partisan book’: applying Edward Said's insights to early modern travel writing

Since its publication in 1978, Edward Said's Orientalism has had a significant impact on postcolonial studies in a range of fields. This paper assesses his impact on the historiography of Anglophone travel writing concerning Ottoman Empire during the early modern period. Said's analysis of the relationship between representational power and colonial authority remains relevant to our understanding of early modern travel texts. Said's epistemology raises significant issues for historians of early modern intercultural encounters. This article summarises recent debates surrounding early modern travel narratives. It contrasts doctrinaire applications of Said's theory with more recent, particularistic studies. It provides a much-needed survey of travel writing historiography that considers the continuing impact of Said's postcolonial thought on the study of early modern travel narratives relating to the Ottoman Middle East. In so doing, it explores the lack of fit between early modern travel narratives and Said's methodology. I explore the methodological problems thrown up by conventional applications of Said's epistemology to precolonial travellers' texts. Based on a wide-ranging survey of Said's oeuvre, the article demonstrates that, more than 30 years on, Said's work remains relevant to the historiographical challenges presented by early modern English travel writing about Islam