Fluorine-18 Patents (2009–2015). Part 1: Novel Radiotracers

Brooks, Allen F.; Drake, Lindsey; Stewart, Megan N.; Cary, Brian P.; Jackson, Isaac M.; Mallette, Dale; Mossine, Andrew V.; Scott, Peter J. H.

doi:10.4155/ppa.15.36

Cited by 12 publications

(2 citation statements)

References 96 publications

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“…However, the rapid growth in nuclear medicine and drug discovery for radiopharmaceuticals poses inherent challenges to radiochemists, since the radiolabeling of many biologically relevant compounds remains difficult. As such, strenuous efforts have been devoted to the development of new radiosynthetic strategies, including the progress from the patents [259][260][261][262] . Over the past decade, these efforts provided a plethora of novel synthetic options and broadened the scope of functional groups that can be harnessed for radiolabeling.…”

Section: Discussionmentioning

confidence: 99%

Radiochemistry for positron emission tomography

et al. 2023

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Positron emission tomography (PET) constitutes a functional imaging technique that is harnessed to probe biological processes in vivo. PET imaging has been used to diagnose and monitor the progression of diseases, as well as to facilitate drug development efforts at both preclinical and clinical stages. The wide applications and rapid development of PET have ultimately led to an increasing demand for new methods in radiochemistry, with the aim to expand the scope of synthons amenable for radiolabeling. In this work, we provide an overview of commonly used chemical transformations for the syntheses of PET tracers in all aspects of radiochemistry, thereby highlighting recent breakthrough discoveries and contemporary challenges in the field. We discuss the use of biologicals for PET imaging and highlight general examples of successful probe discoveries for molecular imaging with PET – with a particular focus on translational and scalable radiochemistry concepts that have been entered to clinical use.

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Section: Discussionmentioning

confidence: 99%

Radiochemistry for positron emission tomography

et al. 2023

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“…48 More recently, Buchwald and co-workers 49 A well-known reaction for the industrial preparation of aryl (and heteroaryl) fluorides is the nucleophilic aromatic substitution (S N Ar). 52 This involves the reaction of an electron-deficient (hetero)aryl halide or nitroarene with a nucleophilic fluoride source to generate the corresponding 13 aryl fluoride. 53a Anhydrous alkali metal fluorides (MF) are most typically employed as the fluoride source (usually CsF).…”

Section: A-conversion Of C Ar -H Into C Ar -F Bondsmentioning

confidence: 99%

Fluorination methods in drug discovery

2016

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Fluorination reactions of medicinal and biologically-active compounds will be discussed. Late stage fluorination strategies of medicinal targets have recently attracted considerable attention on account of the influence that the fluorine atom can impart to targets of medicinal importance, such as a modulation of lipophilicity, electronegativity, basicity and bioavailability, this latter as a consequence of membrane permeability. Therefore, the recourse to late-stage fluorine substitution on compounds with already known and relevant biological activity can provide the pharmaceutical industry with new leads with improved medicinal properties. The fluorination strategies will take into account different fluorinating reagents, nucleophilic, electrophilic and of radical nature. Diverse families of organic compounds such as (hetero)aromatic rings, and aliphatic substrates (sp 3 , sp 2 , and sp carbon atoms) will be studied in late-stage fluorination reaction strategies. The omniphobicity/lipophilicity and electrostatic interactions can be considered among the most prominent effects. Thus, introducing fluorine into an organic compound can significantly alter its biological properties.One other subtle but important effect of introducing fluorine into the backbone of a medicinal target is the inflection of acidity and basicity of the parent compound 4 , which can change, inter alia, the binding affinity, and bioavailability. Highly basic groups can have a detrimental effect on the bioavailability of a drug. Thus introducing a fluorine atom next to a basic group can reduce its basicity, enhancing its membrane permeability, and increasing bioavailability. Although the replacement of hydrogen for fluorine does not have a profound steric influence, electrostatic interactions with other groups can change conformations significantly. The replacement of hydrogen for fluorine on aromatic rings is a well-known strategy to decelerate oxidative metabolic processes by Cytochrome P450 monooxygenases. In this respect, the electron-withdrawing properties of fluorine on aromatic rings, which can slow down hydrolytic metabolism, alter reaction rates and stability of intermediates. Fluorine substitution on aromatic rings is also known to increase binding affinity, as a result of enhancing electrostatic interactions.However, it is difficult to predict the influence of fluorine substitution on the overall profile in a given situation.As numerous reports attest 1 , the number of marketed drugs that contain a fluorine atom has increased rapidly. As of 2009, the FDA-had approved >140 fluorine-containing drugs. This review article is intended to present new synthetic methodologies 9 for accomplishing fluorination reactions on molecules (drugs/prodrugs) with pharmacological activity. It is not our aim (Figure 3). would be beneficial to the syntheses. 3a.-Conversion of C Ar -H into C Ar -F BondsXu and co-workers 38 have developed an ortho C-H bond fluorination of 2-phenoxyl pyridine derivatives through a palladium-catalyzed reaction v...

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