I'm currently coping with qsar analysis of amino-alcohol derivatives of xanthone. In accordance with the best QSAR equation, the position of the substituents were replaced and chlor substituent was added. Later, the new molecule design somehow still got higher IC50 than data sets.
It is depends on your qsar equation, you must
Increase the negative value property of your Substitution selected or decrease the Positive value of your Substitution selected
Hi dear ;
by Using QSAR we find the model that helps us find an interesting and weaker IC50 .
An important consideration in this situation is how much of a difference in IC50 is considered significant. One aspect of the problem is how much variation there is in the IC50 measured for a single compound. That information will tell you how much of a difference in IC50s between any 2 compounds can be considered statistically significant.
Another aspect is whether a statistically significant increase in potency is really an improvement in the compound. There are other considerations in drug design besides IC50. For example, it is frequently possible to lower the IC50 by increasing the hydrophobicity, but this is not necessarily a desirable approach from the point of view of solubility or ADME properties. It may be worth sacrificing some potency to improve the pharmacological aspects of a drug.
Finally, you have to consider how much of a statistically significant change in IC50 is meaningful from a drug design perspective. I have heard it said that a 5-fold decrease is meaningful. Opinions may differ.