Acridine ring

Many antimalarial agents have a common structural feature a quinoline ring or an acridine ring (which is a quinoline ring with an extra benzene ring appended to it). 

The first example of displacement of a chlorine atom on a heterocyclic ring by a phenylacetonitrile derivative was described by Makosza and coworkers.215 The 9-position of the acridine ring (141) is activated because of the two benzo-fused rings. 

Dimethylacridine resiilts from the reaction of 4-metl ldiphenylamine with acetic acid in the presence of zinc chloride the route involves decarboxylation of N-p-tolylanthranilic acid, itself a precursor of the acridine ring system (J.R. Patton and K.H. Dudley. J. heterocyclic Chem., 1979, 16, 257). It is also of interest to note that C-9 of acridine can be introduced directly by the vapour phase reaction of chloroform and diphei lamine (R.E, Busby at., j, chem. Research (M), 1980, 4935). 

The action of amsacrine on DNA soon leads to breaks in DNA strands which causes faulty chromosome segregation at mitosis, and death of the cell follows (Baguley et al., 1981). The strong action on bone-marrow precludes the use of amsacrine in treating solid tumours. These workers have noted that 4,5-disub-stitution in the acridine ring suppresses the bone-marrow effect without loss of cytotoxicity. 

Acridines have continued to be of interest but the Bemthsen reaction has generally been replaced by a stepwise cyclization using transition metal catalyzed amination of aryl ketones or acids followed by acid catalyzed cyclization to form the acridine ring system. ... 

Chiron, J. Galy, J. Reactivity of the acridine ring A review. Synthesis 2004, 313—325. 

NMR experiments showed that 25 and 26 form stronger complexes with ATP than with 24 due to the additional involvement of 7r-stacking interactions between the acridine rings and the nucleic base. 

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