Topliss approach

Genetic programming, a specific form of evolutionary computing, has recently been used for predicting oral bioavailability [23], The results show a slight improvement compared with the ORMUCS Yoshida-Topliss approach. This supervised learning method and other described methods demonstrate that at least qualitative (binned) predictions of oral bioavailability seem tractable directly from the structure. 

Taylor, J (1984) The Topliss Approach—Opinion of an Industrial Scientist on QSAR Methods Lecture given at the Louis Pasteur University, Stasbourg, March 8, 1984. 

Taylor, I. The topliss approach-opinion of an industrial scientist on QSAR methods. Lecture Given at the Louis Pasteur University. Stasbourg New york, 1984. March 8. 

A number of other simple N-acyl derivatives of taxol have been made. Thus Georg prepared various analogs with substituted N-benzoyl groups and analyzed their activity by the Topliss approach (306). She used two different synthetic approaches for this work, employing either... 

Georg GI, Boge TC, Cheruvallath ZS, Harriman GCB, Hepperle M, Park H, Himes RH (1994) Topliss Approach to the Synthesis of Biologically Active Substituted N-Benzoyl Taxol Analogues. Bioorg Med Chem Lett 4 1825... 

Two compounds are selected from the derivatives near the parent compound, prepared, and tested. These are chosen following the Topliss approach [10] that is, by looking for points where one of the parameters is systematically increased or decreased with respect to the original substance, the other remaining constant as far as possible. 

Takayama and Fujinami subsequently prepared seven 3,5-disubsdtuted derivatives, the most potent of which was the 3,5-dibromo (p/50 = 5.77) derivative, which was also the most potent in the whole study. Thus, if the Topliss approach had been followed, 14 compounds, not 61 compounds, would have been prepared, a resource reduction of 77%. Of course, less certainty and thus higher risk would have been involved. For example, no ex-... 

It has been demonstrated that the Topliss approach fails to meet two main criteria for an ideal substituent set wide exploration of available parameter space and a lack of colinearity in factors that are explored. Clearly, the Topliss approach is a high-risk approach that should be considered only in instances in which the specific problem of difficult synthesis is involved. In that case, several cautions should be exercised ... 

Follow-up in the form of a well-designed set based on the constraints learned during the Topliss approach is absolutely required to reduce risk of missing an important compound to an acceptable level. 

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-... 

Of interest is a nonmathematical approach to drug design proposed by Topliss and Topliss and Martin. This concept is based on the fundamental approach of the Hansch concept, namely, that a particular sub-... 

There are two schools of thought in model building. One method is to search for correlations amongst a vast array of physicochemical and structural variables, with no preconceived notion of mechanism. This approach avoids bias and may detect an unexpected relationship, but there is a danger of finding chance relationships that can be misleading (Topliss and Edwards, 1979). The alternative method is to suggest a physical model and make a choice of appropriate descriptors to test that model. 

An essentially nonmathematical approach to utilizing the basic Hansch concepts to help design drugs was developed by Topliss (1977). It has been called a decision tree (Fig. 1-10), by which a lead compound can be efficiently optimized without the use of computers. By preparing several well-chosen analogs of a lead compound, the next several... 

An alternative game plan could be to utilize the Topliss scheme as the initial approach to extract valuable information by the synthesis of a small number of compounds. 

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]. 

The different approaches proposed by Topliss should not be understood as rigid schemes they are strategies which have to be adjusted to each problem. A recent review [403] lists more than 50 references where the Topliss methods have been applied, mostly in medicinal chemistry. It was shown that optimum activity would have rapidly been reached in many series of compounds in accordance with the Topliss scheme [641] on the other hand, there are at least some examples where the Topliss method failed [403, 633]. 

The synthesis and structure-activity studies of schweinfurthin B analogues (264) involved a late stage introduction of the central stilbene part via HWE olefination have been reported. Evidence for the importance of a D-ring hydrogen bond donor in expression of differential cytotoxicity was obtained.The Topliss batchwise approach successfully identified A-2-phenylethylphosphonyl derivative of glutamic... 

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