Synthesis and characterization of polar functional group substituted mono- and bis-(o-carboranyl)-1,3,5-triazine derivatives

Towards carborane-functionalised structures for the treatment of brain cancer

“…Several studies have utilised the synthetic versatility of the nucleophilic 1,3,5triazine ring for the preparation of BNCT agents. Ortho-carboranylthiolatesubstituted 1,3,5-triazines have been synthesised by the research group led by Lee [105], who through the introduction of a further molecular moiety effected improved biological activity through the bestowment of increased aqueous solubility to the structure. Preliminary in vitro studies indicated that many of these triazines effect the highly efficient accumulation of boron to B-16 melanoma cells but are excessively cytotoxic.…”

Modular triazine-based carborane-containing carboxylic acids – synthesis and characterisation of potential boron neutron capture therapy agents made of readily accessible building blocks

“…However, these compounds show only limited water solubility and cellular boron uptake due to unspecific accumulation, caused by the lack of tumour-selective moieties. [22][23][24][25][26][27][28] Another derivative, reported by Ronchi et al, with a β-D-glucose substituent, an ortho-carborane cluster and a cysteine moiety (Chart 1) is remarkably water-soluble and has an amino acid function suitable for coupling reactions with biomolecules. However, the number of synthetic steps required to prepare this compound is rather high (8 steps); thus, the overall yield tends to be very small.…”

“…[33][34][35]36,37 Several carborane-containing s-triazine derivatives have been prepared, also as potential BNCT agents (Chart 1). 22,23,[25][26][27][28][29] The second component are meta-carborane (1,7-dicarbacloso-dodecaborane(12)) derivatives. One problem with orthocarborane derivatives is their facile deboronation under basic conditions.…”

“…As the S, O or N moiety has a higher nucleophilicity as the respective carboxy-Chart 1 Known s-triazine-based carborane derivatives. [22][23][24][25][26][27][28]31 Fig. 1 Combination of a carborane-based building block ( pale red) and carboxylic acid derivatives (blue) with cyanuric chloride (green) as a central branching unit and scaffold to give s-triazine-based carboranecontaining carboxylic acids (E = NH or S; X = CH 2 or (CH 2 ) 4 CHNHBoc (Boc = tert-butoxycarbonyl)).…”

o-Carboranylalkoxy-1,3,5-Triazine Derivatives: Synthesis, Characterization, X-ray Structural Studies, and Biological Activity

“…The medicinal chemistry of o-carborane, which contains ten boron atoms, gives it a clear advantage for use in BNCT [ 15 ]. We previously synthesized 1,2,3,4-tetrahydroisoquinolines [ 16 ], 1,3,5-triazines [ 17 , 18 , 19 ], and piperidines [ 20 , 21 ] containing the o-carborane unit as potential BNCT agents. However, since carborane cages consist only of C–H and B–H units, they have a lipophilic character [ 22 , 23 ].…”