Topliss operational schemes

A real advance in design strategy resulted from the Topliss operational schemes [637, 638]. The Topliss scheme for aromatic substituents (Figure 39) starts from two analogs, e.g. a compound bearing an unsubstituted phenyl ring and the corre-... 

The close relationship between the Topliss operational schemes and art based praaice of many design scientists has made them particularly appealing to those new to the more systematic QSAR approaches. It should be pointed out that few, if any, publications have appeared recently in which the Topliss approach was a primary strategy for optimization. In actual laboratory prac-... 

J.G. Topliss, Application of operational schemes for analog synthesis in drug design. J. Med. Chem., 15 (1972) 1001-1011. 

Figure 4.7 The Topliss decision trees for (a) an unfused aromatic ring and (b) an aliphatic side chain. (L = significantly lower activity, E = about the same activity and M = significantly greater activity). Reproduced by permission of Taylor and Francis Ltd. from the Journal of Medicinal Chemistry 15, No. 101006 (1972), http //www.tandf.co.uk/journals. Utilisation of Operational Schemes for Analog Synthesis in Drug Design by J G Topliss...

A manual method was proposed by Topliss [639] as a modification of his operational schemes a larger number of substituents is selected in the first step to derive the dependence of biological activities on n (linear and nonlinear) and a with a minimum number of analogs. This latter approach has been criticized because of collinearity and unbalanced spanning of the parameter space [640]. 

J. G. Topliss, /. Med. Chem., 15,1006 (1972). Utilization of Operational Schemes for Analog Synthesis in Drug Design. 

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