CARBOCYCLIC COMPOUNDS FUSED TO A BENZENE RING

The nucleus of a modest number of new compounds comprise a two- or three-ring fused system, one of which consists of a benzene ring. As was the case for free-standing benzene rings in Chapter 3, the annelated rings in most instances serve merely as supports for the pharmacophoric substituents. 

The Organic Chemistry of Drug Synthesis, Volume 7. By Daniel Lednicer Copyright 2008 John Wiley Sons, Inc. 

The antidepressant compound lubazodone (8) illustrates the breadth of the structural requirements for serotonin selective reuptake inhibitors the structure of this agent departs markedly from that of fluoxetine, the first drug in this class. The compound at hand also exemplifies the current trend for preparing drugs in chiral form. Thus reaction of the indanol (6) with the mesylate from chiral glycidic oxide in the presence of base leads to the epoxypropyl ether (7) with retention of chirality. Treatment intermediate 7 with aminoethylsulfonic acid closes the morpholine ring. Product 8 consists of pure (5) enantiomer.  

Alzheimer s disease, as noted earlier, is associated with decreased levels of acetyl choline in the brain. Most of the drugs that have been introduced to date for treating this disease thus comprise anticholinergic agents intended to raise the deficient levels by inhibiting loss of existing acetylcholine. A compound-based on an indene perhaps surprisingly, shows 

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We will take a semiempirical approach using numerous molecules, models, assumptions, and estimates rather than doing new calorimetric experiments and/or quantum chemical calculations. Indeed, we will also test what is probably the simplest assumption - that (4n + 2) n electrons found within a conjugated ring species is expected to result in enhanced stability and that this compound is called aromatic. We will consider the dihydroindene (indane) skeleton composed of a benzene ring fused to a nonaromatic five-membered ring that lacks additional double bonds, and will use this carbocyclic hydrocarbon with X = Y = Z = CH2 as a paradigm for many heterocyclic derivatives for which the possible aromaticity is of relevance to the current chapter. Similarly we use indene with -X-Y- = -CH=CH-, Z = CH2 for a variety of unsaturated heterocycles of interest here. 

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