Synthesis and in vivo evaluation of ¹¹C‐labeled (1,7‐dicarba‐closo‐dodecaboran‐1‐yl)‐N‐{[(2S)‐1‐ethylpyrrolidin‐2‐yl]methyl}amide

Abstract

Boron clusters, and especially dicarba-closo-dodecaboranes, can be used as hydrophobic pharmacophores in the design of new drugs and radiotracers because of their hydrophobic character, spherical structure, and excellent chemical and photochemical stability. In the present paper, the synthesis and in vivo evaluation of (11) C-labeled (1,7-dicarba-closo-dodecaboran-1-yl)-N-{[(2S)-1-ethylpyrrolidin-2-yl]methyl}amide, an analog of the D2 receptor ligand [(11) C]raclopride, is described. The radiosynthesis was approached by reaction of the demethylated precursor with [(11) C]CH3 I in basic media; moderate radiochemical yields (18.2 ± 2.8%, decay corrected), and excellent radiochemical purities (>98%) were obtained in overall synthesis time of ~50 min. In vivo assays showed a biodistribution pattern with significant uptake in liver, kidneys and lungs at short times (t = 4 min) after administration and increasing accumulation in bladder at longer times (t ≥ 14.5 min). Although brain positron emission tomography scans showed good blood brain barrier penetration, the high unspecific uptake observed in different brain regions impedes its applicability as D2 receptor ligand.

Synthesis, characterization and radiolabeling of carborane-functionalized tetrazines for use in inverse electron demand Diels–Alder ligation reactions

“…They have also been used as boron-rich bioconjugates, including antibody-linked clusters [38]. Carboranes have also been used to prepare radiopharmaceuticals, stemming from their ability to be radiolabeled with a range of medical isotopes including carbon-11 [39], fluorine-18 [40], bromine-76 [41], iodine-125 and -123 [9,[42][43][44], astatine-211 [45][46][47][48] and technetium-99m [49,50].…”

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

“…Dicarbadodecaboranes (carboranes) are known to be 3D polyhedral clusters with a special type of structural organization, relative thermal and chemical stabilities, as well as unique physicochemical properties [ 1 – 3 ]. The functional derivatives of carboranes, in particular heterocyclic ones, are undeniably of increased interest in the chemistry of organoboron compounds due to wide opportunities to use these boron-enriched substances as diagnostic tools for tumor radio imaging [ 4 – 7 ], promising agents for boron neutron capture therapy (BNCT) of cancer [ 8 – 12 ], as well as agonists and antagonists of biological receptors [ 13 – 17 ], etc. In addition, azaheterocyclic carboranes are actively used as ligands in the synthesis of metal complexes of various architectures, possessing catalytic activity [ 18 – 21 ], as well as unique photophysical properties [ 22 – 26 ].…”

Synthesis of Dicarba-closo-dodecaborane-1-carboxamides

“…Classical amide bond formation via the carboxylic acid chloride is possible. However, only moderate yields were reported, and the procedure was time-consuming, requiring hazardous chlorinating agents and the isolation of carborane-1-carbonyl chloride needing laborious distillation. ,, The latter renders low-scale reactions difficult, which is a clear drawback, in particular for reactions with the expensive p -carborane. Thus, other routes to the generation of carboranylamides have been investigated in the recent past.…”