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J G Topliss

Publications and source records attributed to J G Topliss.

11 recordsLinked to original sources
PubMed1979

Chance factors in studies of quantitative structure-activity relationships.

Multiple regression analysis is a basic statistical tool used for QSAR studies in drug design. However, there is a risk or arriving at fortuitous correlations when too many variables are screened relative to the number of available observations. In this regard, a critical distinction must be made between the number of variables screened for possible correlation and the number which actually appear in the regression equation. Using a modified Fortran stepwise multiple-regression analysis program, simulated QSAR studies employing random numbers were run for many different combinations of screened variables and observations. Under certain conditions, a substantial incidence of correlations with high r2 values were found, although the overall degree of chance correlation noted was less than that reported in a previous study. Analysis of the results has provided a basis for making judgements concerning the level of risk of encountering chance correlations for a wide range of combinations of observations and screened variables in QSAR studies using multiple-regression analysis. For illustrative purposes, some examples involving published QSAR studies have been considered and the reported correlations shown to be less significant than originally presented through the influence of unrecognized chance factors.

Computers↗
PubMed1977

A manual method for applying the Hansch approach to drug design.

A procedure is described in which an initial small group of compounds is selected, tested, and ordered according to potency. The potency order in the group is then compared to the tabulated potency order calculated for various parameter dependencies relating to hydrophobic, electronic, and steric effects. From this activity pattern analysis the probable operative parameters can be deduced and a new substituent selection made for the synthesis of potentially more potent analogues. Application of the method is illustrated with a series of examples. It differs from a previously described decision tree, single compound stepwise approach in that it involves the batchwise analysis of small groups of compounds, usually the preferred procedure for logistical reasons if the compounds are relatively easy to synthesize.

Alcohol Oxidoreductases↗
PubMed1975

Quantitative structure-activity relationships in the delta6-6-substituted progesterone series. A reappraisal.

A quantitative structure-activity analysis concerning the progestational activity of a series of delta6-6-substituted progesterone is presented which differs from that published recently by other authors. In the current study all compounds in the data set for which parameters are available are included and activity is shown to relate to primarily lipophilic but also steric effects.

Kinetics↗