Dibenzo Heterocycles Containing One Ring Nitrogen Atom

Dibenzo Heterocycles Containing One Ring Nitrogen Atom 

The devastating mental deterioration that characterizes Alzheimer s disease has been attributed to a mishandling of the neurotransmitter acetylchohne. Inhibitors of acetylcholinesterase, the enzyme that catabolizes that substance, would be expected to help restore deficient acetylcholine levels. Several partly reduced acridines have shown some activity in treating Alzheimer s disease. At least one of these, tacrine (14-5), is now approved for use in patients. The initial step in the synthesis of the first of these consists of the sodium amide catalyzed condensation of isatin (14-1) with cyclohexanone. The reaction can be visualized by assuming the first step to involve an attack of amide on isatin to give an amido-amide such as (14-2) (note that no attempt has been made to account for charges). This can then react with 

The nitrogen mustards, compounds that incorporate a few-chloroethylamino moiety, have a venerable history as cytotoxic agents used in cancer chemotherapy. 

Ring expansion of more readily accessible acridines provides an alternate method for preparing the dibenzazepines. The starting halide (18-1) can be obtained by chlorination of the corresponding A -acetyl dihydroacridine. The displacement of 

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