The story behind Oncotarget? A bibliometric analysis

Being the most proliferative journal of oncology a cancer research of the past decade, the Open Access journal Oncotarget had reached more than 20,000 publications and a relatively high impact factor score in the past years. In 2018, the journal citation report decided to withdraw the status of an impact factor journal. Since there was a large discussion in the scientific community and specific reasons for the withdrawal were not stated, this bibliometric analysis was performed to assess if Oncotarget exhibits any differences in its bibliometric structure compared to other journals. For this purpose, we used the “New Quality and Quantity Indices in Sciences” platform and analyzed 20,000 Oncotarget articles. Density equalizing mapping technique helps to construct maps of cancer research in Oncotarget and shows that it has led to a unique global landscape which is not asymmetrically dominated by the Western hemisphere but exhibits a publishing architecture with a pronounced emphasis on Chinese articles.

     

Predicting and tuning physicochemical properties in lead optimization: amine basicities

This review describes simple and useful concepts for predicting and tuning the pK(a) values of basic amine centers, a crucial step in the optimization of physical and ADME properties of many lead structures in drug-discovery research. The article starts with a case study of tricyclic thrombin inhibitors featuring a tertiary amine center with pK(a) values that can be tuned over a wide range, from the usual value of around 10 to below 2 by (remote) neighboring functionalities commonly encountered in medicinal chemistry. Next, the changes in pK(a) of acyclic and cyclic amines upon substitution by fluorine, oxygen, nitrogen, and sulfur functionalities, as well as carbonyl and carboxyl derivatives are systematically analyzed, leading to the derivation of simple rules for pK(a) prediction. Electronic and stereoelectronic effects in cyclic amines are discussed, and the emerging computational methods for pK(a) predictions are briefly surveyed. The rules for tuning amine basicities should not only be of interest in drug-discovery research, but also to the development of new crop-protection agents, new amine ligands for organometallic complexes, and in particular, to the growing field of amine-based organocatalysis.     

Fluorine in medicinal chemistry

Fluorinated compounds are synthesized in pharmaceutical research on a routine basis and many marketed compounds contain fluorine. The present review summarizes some of the most frequently employed strategies for using fluorine substituents in medicinal chemistry. Quite often, fluorine is introduced to improve the metabolic stability by blocking metabolically labile sites. However, fluorine can also be used to modulate the physicochemical properties, such as lipophilicity or basicity. It may exert a substantial effect on the conformation of a molecule. Increasingly, fluorine is used to enhance the binding affinity to the target protein. Recent 3D-structure determinations of protein complexes with bound fluorinated ligands have led to an improved understanding of the nonbonding protein-ligand interactions that involve fluorine.