Interconnection of sulfides and sulfoxides in medicinal chemistry. Issue 1 (6th December 2018)

• Record Type: Journal Article
• Authors: Surur, Abdrrahman Shemsu; Schulig, Lukas; Link, Andreas
• Is Part Of: Archiv der Pharmazie. Volume 352:Issue 1(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-12-06
• Subjects: antituberculosis activity -- inhibitors -- oxidation kinetics -- rational drug design -- sulfides -- sulfoxides; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201800248
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: Aromatic heterocycles with basic nitrogen atoms as well as carboxylic acid derivatives are the dominating chemical space in the universe of drug‐like molecules. These established and exceedingly evaluated structural motifs have to be combined with elements of diversity in order to chart less well‐explored galaxies of chemical space and to be able to tackle seemingly undruggable targets. Flat scaffolds should be replaced by shapely molecular cores. In this context, it has been unheeded that phenyl rings in diaryl sulfides are less co‐planar than in ethers and that the metabolic interconnection of sulfides and sulfoxides offers advantages that are unalike from the chemistry of amines and N‐oxides in the CHN‐O world. Moreover, σ‐hole potentials increase with the polarizability of the atom N < P < O < S and do not only play a role in long‐time overlooked halogen bonds. Examples for λ 2, λ 4, and λ 6 S‐based functionalities related to improved solubility, reduced drug resistance, linkers in drug conjugates, drug‐targeting to parasites, and as basis for drug monitoring in sports are given and discussed. Abstract : Aromatic heterocycles with basic nitrogen atoms and carboxylic acid derivatives dominate the chemical space of drug‐like molecules. These established structural motifs have to be combined with elements of diversity in order to be able to tackle seemingly undruggable targets. Examples for functionalities related to improved solubility, reduced drug resistance, linkers in drug conjugates, and drug‐targeting to parasites are discussed.