Data analysis of MMP “from OR to Fluorine” #memo #journal

Control lipophilicity is key strategy for drug design. Medicinal chemist often struggle to ADMET issue due to their compound lipophilicity. Sometime ADMET issue can be improved by reducing LogD but it cause loss of potency. Matched molecular pair approach is used to find bioisosteric replacements that mean the substructure replacement with keeping potency but change molecular properties.

Yesterday, I read an interesting article from JMC.

The title was ‘Effects of Replacing Oxygenated Functionality with Fluorine on Lipophilicity’.

https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.1c00668

The author analysed specific substructure pairs, such as from methoxy to fluorine, hydroxy to fluorine of various substituted aromatic ring compounds.

And they found that the effect of OR to F replacement is affected by substituents on the aromatic ring.

Fig2 and Fig3 show clear view of substituents effect. I think it’s worth to remind for drug design. If reader who has interest the article please check it.

Large amount of data is required to find the trend like the article but after finding it we can apply the rule to new compound design.

nani gigantum umeris insidentes

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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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