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A comprehensive study of physicochemical properties (pKa, LogP, and intrinsic microsomal clearance) within the series of mono‐ and difluorinated azetidine, pyrrolidine, and piperidine derivatives was performed. While the number of fluorine atoms and their distance to the protonation center were the major factors defining the compound's basicity, both pKa and LogP values were affected considerably by the conformational preferences of the corresponding derivatives. For example, features of "Janus face" (facially polarized) cyclic compounds (i. e., unusually high hydrophilicity) were identified for cis‐3,5‐difluoropiperidine, preferring a diaxial conformation. Intrinsic microsomal clearance measurements demonstrated high metabolic stability of the compounds studied (with a single exception of the 3,3‐difluoroazetidine derivative). According to pKa – LogP plots, the title compounds provide a valuable extension of the fluorine‐containing (e. g., fluoroalkyl‐substituted) saturated heterocyclic amine series as building blocks for rational optimization studies in early drug discovery. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis and reactions of a new diazoalkane reagent called (diazomethyl)dimethylphosphine oxide (Me₂P(O)CHN₂). Ukrainian chemists have extensively studied various diazoalkanes relevant to medicinal chemistry over the past two decades. The research article by O. O. Grygorenko and co-workers provides more information on the synthesis and [3+2] cycloaddition reactions of this novel diazoalkane reagent. The article also includes artwork by Vitalii Boklashchuk. [Extracted from the article]

All pharmaceutical products contain organic molecules; the source may be a natural product or a fully synthetic molecule, or a combination of both. Thus, it follows that organic chemistry underpins both existing and upcoming pharmaceutical products. The reverse relationship has also affected organic synthesis, changing its landscape towards increasingly complex targets. This Review article sets out to give a concise appraisal of this symbiotic relationship between organic chemistry and drug discovery, along with a discussion of the design concepts and highlighting key milestones along the journey. In particular, criteria for a high‐quality compound library design enabling efficient virtual navigation of chemical space, as well as rise and fall of concepts for its synthetic exploration (such as combinatorial chemistry; diversity‐, biology‐, lead‐, or fragment‐oriented syntheses; and DNA‐encoded libraries) are critically surveyed. [ABSTRACT FROM AUTHOR]

Front Cover: Effect of gem-Difluorination on the Key Physicochemical Properties Relevant to Medicinal Chemistry: The Case of Functionalized Cycloalkanes (Chem. Eur. J. 19/2022) Fluorine, cycloalkanes, lipophilicity, acidity and basicity, metabolic stability Keywords: fluorine; cycloalkanes; lipophilicity; acidity and basicity; metabolic stability EN fluorine cycloalkanes lipophilicity acidity and basicity metabolic stability 1 1 1 04/05/22 20220401 NES 220401 B The CF SB 2 sb dragon reborn b !. [Extracted from the article]