Benzofused rings

The Pfizer team started with sertraline, a Pfizer product that was already well understood with regard to which functional groups were required for high activity. Initial efforts focused on the benzofused ring of sertraline. Substitution of a polar sulfonamide group was hoped to decrease both Vd and tv. Compound 8.67 showed... 

Particularly, benzofused Cp derivatives such as indene and fluorene had serious impact on the development of catalyst precursors for stereospecific olefin polymerization [17]. However, fusing aromatic ring systems to the cyclo-pentadienyl ring can sometimes cause problems with regard to the bonding situation between metal and ligand because the tendency of the benzofused ring to preserve its aromatic six-electron system leads to a haptotropic shift as depicted in Scheme 6.2. 

TbfnCl2(2,6-Me2C6H30) (XVI) is well soluble in dichloromethane and THF, is of low solubility in toluene, and is completely insoluble in aliphatic solvents. It could be isolated in 21% yield as red crystals with four molecules per unit cell in the monoclinic crystal system P2i/c. As listed in Table 6.3, the Ti-Ct distance measures 2.0701 A, and the Ti-Cl bond lengths amount to an average of 2.270 A (Fig. 6.12). Like in compound XV also in XVI it is to assume that face-to-face n-stacking interactions take place between the benzofused ring C12-C17 and the phenoxide ring C30-C35 as the distance between its respective centroids measures 3.62 A. 

A diversity of biological effects are possessed by benzofused six-membered heterocycles. These range from antimicrobial activity to cardiovascular, CNS, and inflammation-influencing agents. It can be inferred that the ring system itself is primarily a molecular scaffold upon which to assemble the characteristic pharmacophore for the various receptors involved. It is interesting also to note that the range of bioactivities involved differ substantially from those seen with the benzofused five-membered heterocycles described in Chapter 10. 

Chapter 7. Five-Membered Ring Benzofused Heterocycles... 

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