Compound quality for drug discovery

I think there are some approaches to start drug discovery project.

  1. HTS, 2. Phenotypic screening, 3. FBDD, 4. Me too (Patent) etc.

We have to improve succeed rate of screening. So, compound quality is key factor.
Because good starting point is key for compound quality.
Serge et. al. published good review in drug discovery today. URL is following.

There are lots of indicators about drug likeness. For example Ro5, Ro3, QED, Golden Triangle etc. Some indicators are publicly-available. I consider about some rules in my project.

In the review, the author described about entropy and enthalpy.
I’m interested in entropy and enthalpy driven compound optimisation. These data tells chemist more details of binding affinity.

The entropic contribution relies on favorable but non-specific interaction. It causes molecular obesity.
And the enthalpic contributions relies of specific geometric complementarity between drug and target. It’s difficult to design. But we need control these interactions.

So, I think medchem take care about why the affinity is changed?
But, I have a question about entropy/enthalpy driven optimisation process.
If there are no structural data, can we understand details about interaction between drug and target, can we design molecule with suitable direction of the substituents ?

I think many compounds are needed to understand ligand-target interactions in the case of the above.

Recently medchem can access lots of indicators and in vitro data and are required rapid decision.

Who do you think about quality of compound?

Published by iwatobipen

I'm medicinal chemist in mid size of pharmaceutical company. I love chemoinfo, cording, organic synthesis, my family.

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