Fluorine-containing amines and amino acids with reduced conformational flexibility
Fluorinated organic compounds are of high interest in biochemistry, medicinal chemistry, and pharmacology. In many cases the replacement of a hydrogen atom with fluorine in a drug molecule caused 10-fold increase of its biological potency and bioavailability.
Fluorine-substituted amines and amino acids have been extensively used as important building blocks in the design of drugs with a broad spectrum of biological activities. Indeed, the fluorine atom normally lowers basisity of the amine functionality, decreases acute toxicity, and increases the metabolic stability of a target drug.
Today much attention of medicinal chemists is paid to structural analogues of naturally occurring amines and amino acids in which conformational freedom is substantially reduced by the presence of small rings. It is postulated that in living organisms these cyclic compounds have reduced metabolism compared with their open-chain congeners. Introduction of fluorinated fragments into the cyclic amines could in turn trigger their metabolic activity. Recent literature examples collected in Figure 1 show the synthetic utility of shape-persistent fluorine-containing amines in drug discovery.
Activator of ATP-sensitive potassium channels
Highly potent histamine H3 receptor antagonist
Enamine offers a collection of shape-persistent fluorine containing amines and amino acids for drug discovery. You can download the database of 138 representative rigid fluorinated amines and amino acids or browse through the set on-line. Several examples of compounds from this set are presented below: