Among carbon, hydrogen, oxygen, and nitrogen, sulfur and fluorine are both leading constituents of the pharmaceuticals that comprise our medicinal history. In efforts to stimulate the minds of both the general public and expert scientist, statistics were collected from the trends associated with therapeutics spanning 12 disease categories (a total of 1969 drugs) from our new graphical montage compilation: disease focused pharmaceuticals posters. Each poster is a vibrant display of a collection of pharmaceuticals (including structural image, Food and Drug Administration (FDA) approval date, international nonproprietary name (INN), initial market name, and a color-coded subclass of function) organized chronologically and classified according to an association with a particular clinical indication. Specifically, the evolution and structural diversity of sulfur and the popular integration of fluorine into drugs introduced over the past 50 years are evaluated. The presented qualitative conclusions in this arti...

Data-mining for sulfur and fluorine: an evaluation of pharmaceuticals to reveal opportunities for drug design and discovery.

Good Partnership between Sulfur and Fluorine: Sulfur-Based Fluorination and Fluoroalkylation Reagents for Organic Synthesis

The addition of a radical to a heteroaromatic base is commonly referred to as a Minsici reaction. Such reactions constitute a broad-set of selective CH-functionalization processes. This review describes some of the major applications of Minisci reactions and related processes to medicinal or biological chemistry, and highlights some potential developments within this area.

Minisci reactions: Versatile CH-functionalizations for medicinal chemists

The applications of fluorine in drug design continue to expand, facilitated by an improved understanding of its effects on physicochemical properties and the development of synthetic methodologies that are providing access to new fluorinated motifs. In turn, studies of fluorinated molecules are providing deeper insights into the effects of fluorine on metabolic pathways, distribution, and disposition. Despite the high strength of the C-F bond, the departure of fluoride from metabolic intermediates can be facile. This reactivity has been leveraged in the design of mechanism-based enzyme inhibitors and has influenced the metabolic fate of fluorinated compounds. In this Perspective, we summarize the literature associated with the metabolism of fluorinated molecules, focusing on examples where the presence of fluorine influences the metabolic profile. These studies have revealed potentially problematic outcomes with some fluorinated motifs and are enhancing our understanding of how fluorine should be deployed.

Metabolic and Pharmaceutical Aspects of Fluorinated Compounds.

Preparation and utility of organic pentafluorosulfanyl-containing compounds.

Two novel SF5 analogs of the antimalarial agent mefloquine were synthesized in 5 steps and 10–23% overall yields and found to have improved activity and selectivity against malaria parasites. This work also represents the first report of SF5-substituted quinolines.

Synthesis and biological evaluation of the first pentafluorosulfanyl analogs of mefloquine

Synthesis of an 8-pentafluorosulfanyl analog of the antimalarial agent mefloquine

The present invention relates to new mefloquine derivatives and therapeutic compositions comprising one or more mefloquine derivatives. Mefloquine derivatives of the invention have a pentafluorosulfanyl moiety substitution at the 8-position. Certain mefloquine derivatives further include a quinoline methanol moiety substitution at the 4-position. The present invention also relates to new intermediate compounds useful in the synthesis of the mefloquine derivatives, which intermediates also have a pentafluorosulfanyl moiety substitution at the 8-position.

Derivatives of mefloquine and associated methods for making and using

The present invention relates to new mefloquine derivatives and therapeutic compositions comprising one or more mefloquine derivatives. Mefloquine derivatives of the invention have at least one pentafluorosulfanyl moiety substitution at the 6 or 7 or 8 position. Certain mefloquine derivatives further include a quinoline methonal moiety substitution at the 4 position. These compositions are useful in the reduction, treatment, or prevention of malaria, microbial, parasitic, protozoan, bacterial, and fungal diseases and conditions. Advantageously, compositions of the invention are less able to cross the blood-brain barrier than mefloquine and as a result produce fewer adverse side effects to the central nervous system as compared to mefloquine.

Tingting Mo

Papers

Synthesis and biological evaluation of the first pentafluorosulfanyl analogs of mefloquine

Synthesis of an 8-pentafluorosulfanyl analog of the antimalarial agent mefloquine

Derivatives of mefloquine and associated methods for making and using

Pentafluorosulfanyl analogs of mefloquine