Aromatic ring count

Table 2 Table of mean aromatic ring count in the Glaxo-SmithKline pipeline... 

Ritchie, T.J. and Macdonald, S.J.F. (2009) The impact of aromatic ring count on compound developability are too many aromatic rings a liability in drug design Drug Discovery Today, 14, 1011-1020. 

A recent study has shown that aromatic ring count is a significant factor in compound developability [53]. 

Calculated properties were restricted to ClogP <3, the number of rotatable bonds <5, the number of hydrogen bond acceptors (HBA) <4 and the number of hydrogen bond donors (HBD) between 1 and 3. The topological polar surface area (TPSA) was set to <70 A2. In addition, a special feature count excludes structures that are too functionalised (feature rich) or dull (absence of pharmacophoric interaction points). This feature count is the sum of HBA, HBD and the number of five-and six-membered aromatic rings and selection was restricted to fragments with a feature count in the range 4-7. 

In the DGEBA product (n = 1) shown in Fig. 3.13, the epoxy groups are separated by seven units (the aromatic ring is counted as one unit). In other resins the groups may be... 

By chain backbone is understood the polymer chain proper without side groups and branches. For instance, all vinyl polymers have two atoms per structural unit in the chain backbone. If an aromatic ring is part of the backbone, Z is counted as follows o-phenylene, Z = 2 m-phenylene, Z = 3 p-phenylene, Z = 4. For alicyclic rings the same rule is applied. 

Resolvable biphenyls must contain two different ortho substituents on each ring (hydrogen can, of course, count as a substituent, though it is diminutive). If one, or both, rings contain two identical substituents, the molecule is not chiral. In order to make this point clear, consider the molecule 11 and make a model of it. In 11 the molecule is represented in a key conformation with the two aromatic rings mutually perpendicular. 

The stability of the sigma complex is the guiding principle when determining the site of electrophilic attack on any aromatic ring. The more approximately equal energy resonance structures the carbocation has, generally the more stable it is. Resonance forms that place the positive charge next to an ewg are poor and should not be counted. 

Nq-c is the number of carbon-carbon double bonds in the repeat unit, excluding any such bonds found along the edges of rings. For example, the purely formal double bonds in valence bond representations of aromatic rings, as well as carbon-carbon double bonds in any other type of ring structure, are not counted in Nc=c-... 

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