Applications of Fluorine in Medicinal Chemistry.

Journal of medicinal chemistry (2015-07-23)
Eric P Gillis, Kyle J Eastman, Matthew D Hill, David J Donnelly, Nicholas A Meanwell
ABSTRACT

The role of fluorine in drug design and development is expanding rapidly as we learn more about the unique properties associated with this unusual element and how to deploy it with greater sophistication. The judicious introduction of fluorine into a molecule can productively influence conformation, pKa, intrinsic potency, membrane permeability, metabolic pathways, and pharmacokinetic properties. In addition, (18)F has been established as a useful positron emitting isotope for use with in vivo imaging technology that potentially has extensive application in drug discovery and development, often limited only by convenient synthetic accessibility to labeled compounds. The wide ranging applications of fluorine in drug design are providing a strong stimulus for the development of new synthetic methodologies that allow more facile access to a wide range of fluorinated compounds. In this review, we provide an update on the effects of the strategic incorporation of fluorine in drug molecules and applications in positron emission tomography.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cholesterol, Sigma Grade, ≥99%
Sigma-Aldrich
Tetrabutylammonium fluoride solution, 1.0 M in THF
Sigma-Aldrich
Ammonium chloride, for molecular biology, suitable for cell culture, ≥99.5%
Sigma-Aldrich
Cholesterol, powder, BioReagent, suitable for cell culture, ≥99%
Sigma-Aldrich
Ammonium chloride, 99.998% trace metals basis
Sigma-Aldrich
Ammonium chloride, ReagentPlus®, ≥99.5%
Sigma-Aldrich
Diphenylphosphine, 98%
SAFC
Cholesterol, Plant-Derived
Sigma-Aldrich
SyntheChol® NS0 Supplement, 500 ×, synthetic cholesterol, animal component-free, aqueous solution, sterile-filtered, suitable for cell culture
Sigma-Aldrich
N-Methyl-D-aspartic acid, ≥98% (TLC), solid
Sigma-Aldrich
Cholesterol, from sheep wool, ≥92.5% (GC), powder
Sigma-Aldrich
Tantalum(V) ethoxide, 99.98% trace metals basis
Supelco
Cholesterol solution, certified reference material, 10 mg/mL in chloroform
Sigma-Aldrich
Tetrabutylammonium fluoride solution, 75 wt. % in H2O
Sigma-Aldrich
Ammonium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
Ammonium chloride, 99.99% trace metals basis
Sigma-Aldrich
Ammonium chloride, puriss., meets analytical specification of Ph. Eur., BP, USP, FCC, 99.5-100.5% (calc. to the dried substance)
Sigma-Aldrich
Tetrabutylammonium fluoride on silica gel, ~1.5 mmol/g (F-)
SAFC
Cholesterol, from sheep wool, Controlled origin, meets USP/NF testing specifications
Tantalum(V) ethoxide, packaged for use in deposition systems
Sigma-Aldrich
Ammonium-14N chloride, 99.99 atom % 14N, 15N-depleted, 99% (CP)