Exploration of the structure–activity relationship of a novel tetracyclic class of TSPO ligands—Potential novel positron emitting tomography imaging agents

2-[18F]Fluoroethyl tosylate – a versatile tool for building18F-based radiotracers for positron emission tomography

“…86,87,89 In a number of protocols besides the [ 18 F]fluoroethylation with [ 18 F]FETs (indirect approach), the direct radiolabeling of a corresponding mesylated or tosylated precursor with [ 18 F]fluoride has been performed in a parallel approach. By comparison of these two synthesis pathways, it is shown at first glance that in several protocols, direct [ 18 F] fluorination with [ 18 F]fluoride provided more than doubled overall yields compared to [ 18 F]fluoroethylation [93][94][95]97,98,103 suggesting the direct method as the superior one. However, in a closer look, it turned out that often the RCY of [ 18 F]fluoroethylation was diminished by the use of e.g.…”

“…In contrast, the direct nucleophilic substitution of a tosylated precursor of NS14490 with of a radioligand for the translocator protein (TSPO), which is an established target for the imaging of neuroinflammation with PET. 98 For the indirect pathway, [ 18 F]FETs was reacted with the indole in DMF in the presence of sodium hydride for 10 min at 100°C (Fig. 58).…”

Fluorine-18 labelled building blocks for PET tracer synthesis

“…Numerous N-alkylations with [ 18 F]FETos have been performed (Scheme 22). 49,57,[82][83][84][85][86][87][88][89][90][91][92][93][94][95] General reaction conditions involve the use of polar aprotic solvents such as DMSO, DMF or MeCN and temperatures ranging from 82 to 130 1C. Mostly, inorganic bases with a range of different pK a -values were employed depending on the reactivity of the corresponding amine reactant.…”

“…Radiolabelled 61 and 64 are important PET tracers for translocator protein and VEGF, respectively. 85,90 Studies that involve Finkelstein-type alkylation reactions by addition of alkali iodides showed promising results indicating that in situ iodide exchange indeed could increase the yield of N-alkylation. 96 However, this strategy has only been applied to access the serotonin 4 receptor tracer 60 and actually did not appear beneficial for the overall reaction outcome.…”

Acetamidobenzoxazolone scaffold as a promising translocator protein (18 kDa, TSPO) marker for neuroinflammation imaging: Advancement in last decennial period

“…In an effort to search pharmacophore having TSPO selective binding potential (BP) over central benzodiazepine receptor (CBR), several structure‐activity relationship (SAR) analyses have been done in the past (Barresi et al, 2021; Singh et al, 2022). Sailing through these studies the most established the initial pharmacophore that have come up in frontline were 4‐phenylquinazoline‐2‐carboxamides, pyrazolopyrimidines, tricyclic‐indoles, N , N ‐dialkyl‐2‐phenylindol‐3‐ylglyoxylamide (PIGA), N ‐ sec ‐butyl‐4‐(2‐chlorophenyl)‐Nmethylquinazoline‐2‐carboxamide and benzoxazolone (Castellano et al, 2012, 2014; Fukaya et al, 2013; Ikawa et al, 2017; F. Li et al, 2016; O'Shea et al, 2013; Pike et al, 2011; Siméon et al, 2021; Tang et al, 2013; Wadsworth et al, 2012; Zanotti‐Fregonara et al, 2014). The foremost PET ligands representative of these pharmacophore were ( R )[ 11 C]PK11195, [ 11 C]DPA713/[ 11 C]DPA714, [ 18 F]GE‐180, FGIN‐1, and [ 18 F]FEBMP, respectively.…”