4.5.9- Trisubstituted acridines

Apart from 2,6,9-trisubstituted acridines described above, 2,4,9-trisubstituted acridines have been prepared and examined (c Scheme 9). The syntheses of... 

Structural model of the complex of the 3,6,9-trisubstituted acridine ligand (3) with the intramolecular basket quadruplex structure of the human telomeric sequence, (a) End-stacking with the terminal G-tetradpermits the substituent at the 9-position to interact with the flexible TTA loop structure in a specific manner, (b) X-ray structure of the complex of a di-substituted aninoalkylamido acridine (4) with the dimeric hairpin quadruplex structure derived from the Oxytricha nova sequence d(GGGGTTTTGGGG)2. The drug end-stacks and interacts extensively with the thymine loop ((a) Adapted from ref 25 and (b) from RCSB Protein Data Bank co-ordinates ILIH (ref 49)). 

Extending this approach to the design of 3,6,9-trisubstituted acridine ligands... 

G-quadruplex ligands from the trisubstituted acridine series were also found to inhibit in vitro the unwinding by the RecQ helicases, BLM and WRN. Therefore, because of their additional effects on RecQ helicases, these ligands should also disrupt telomere synthesis (Figure 11). In addition, their action against other G-quadruplex resolvases during replication might provoke DNA... 

Using Upjohn condition (OsOi-NMO). The utility of the Upjohn protocol for the dihydroxylation was recently demonstrated in the synthesis of bicyclic analogues of pentopyranoses, (-)-anisomycin, trisubstituted y-butyrolactone, 6-bromo-4-(l,2-dihydroxyethyl)-7-hydroxycoumarine (Bhc-diol) as a photoremovable protecting group, 3,4-dihydroxy-2-(3-methylbut-2-enyl)-3,4-dihydronaphthalen-l(2//)-one, benzo-[c]pyrano[3,2-/z]acridin-7-ones, both enantiomers of conduri-tol C tetraacetate and of mei o-conduritol-D-tetraacetate. ... 

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