Cobalt-mediated solid phase synthesis of 3-O-alkynylbenzyl galactosides and their evaluation as galectin inhibitors

Glycomimetics versus Multivalent Glycoconjugates for the Design of High Affinity Lectin Ligands

“…3-(1,2,3-Triazolyl)-β- d -thiogalactosides have also been reported (Table , entry 26) and provided inhibitors with micromolar K d values . Another strategy used alkylation at the 3-position of galactose , (Table , entries 27,28) or 3′-position of LacNAc (Table , entry 29) with hydrophobic benzyl ethers leading to moderate to strong enhancement of affinities toward both Gal-1 and -3. Nevertheless, the LacNAc scaffold with an additional hydrophobic phthalimido substituent at the 2-position provided the best results not only in terms of affinity but also in terms of selectivity between Gal-1 and -3 (more than 230 in favor of Gal-3), which is another challenge in such drug design approaches.…”

Functions and Inhibition of Galectin-7, an Emerging Target in Cellular Pathophysiology

“…They found two of them to be the simple straight-chain allyl- and hydroxymethyl-substituted alkynes 13 and 14 , which suggests that the binding pocket of galectin-7 close to galactose O-3 is relatively small and does not allow larger cyclic structures to bind. The K d (mM) values against galectin-1, -3, -7, -8N and -9N were measured in a competitive fluorescence polarization assay and listed in Table 3 [ 117 ]:…”

“…Compound 13 proved to be the most interesting inhibitor, due to its lowest K d value and its selectivity. Compared to affinities for other members of the galectin family, preference for galectin-7 is increased by a factor of up to 100 [ 117 ].…”

Combinatorial Chemistry Online

“…The polymer-bound carbohydrate substrate was cleaved from the resin with different carbon nucleophiles in a cobalt-mediated Nicholas reaction. 5 A facile method for the solid-phase synthesis of pyrrolo [2,1-c] [1,4]benzodiazepine dimers has been developed. p-Nitrophenyl carbonate Wang resin attached to 2-amino-5-methoxy-methyl benzoate has been utilised as the resin-bound starting material and these reactions were monitored by FT-IR spectroscopy of resin beads.…”