para-chlorophenyl is favor than others ?

Cl-Phenyl group is often used in medicinal chemistry. There are three attachment point, ortho, meta, para.
Which position do you like ?
This article analysed about the effect of paraCl-Pheny from lots of view points.
The author is developer of ‘MATSY’. I think “MATSY” is cool ;-).
In AstraZeneca, medicinal chemist prefer para-Cl than metha, and ortho.
This trend is found in public or commercial DB, ChEMBL, ACD, IBEX, Drugs. This trend is different from pyridine, CF3-Ph ( more detail check article.).
Where the bias comes from?
Does it come from Topliss decision tree?
A good pdf is following link http://www.maybridge.com/Images/pdfs/MedChem_Vol2.pdf.
The authors analysed about effect of paraCl for DMPK, cost, protein-ligand interaction.

Also analysed from HTS campaign.
Then they said..
A chemist who might see the data for one of these screens without knowledge of the
collection bias may be tempted to conclude that their target favors p-ClPh substitution over the other regioisomers.

Hmm.. How about our library? Do it have same biases ??

And I agree following opinion.
Why chemist are not fully aware of paraCl biases ?
One reason is that the medicinal chemistry
community as a whole has not yet integrated detailed statistic
studies into decision making.

I want to design molecules more rational, make strategy using statistics and improve medicinal chemistry.

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