What are the criteria of Lipinski's rule Sertindole does not fulfill?
It says in my textbook that Lipinski's rules are more strict when talking about drugs where the brain is the target, whereas the first rule is that a drug should have a moleculeweight of under 400 g/mol as oppesed to the 500 g/mol limit set by lipinski´s generel rules. The molecule weight of the drug in question is 440.991 g/mol.
However I cannot see these more strict rules when I am reading about Lipinski's rules online. Perhaps it is not something used otherwhere than in my textbook?
But even if that is the case, the molecule still lays outside of the golden triangle plot. The drug's logD is caluclated as being 2.96 at pH 7.4.
Lipinski and McKerrow coauthored a short article in 2017 that noted that some antiparasitics and fungicides fell outside the rule of five. That particular point does not apply here, but IMO one has to be cautious not to throw the baby out with the bath more generally. Obviously it is a worthwhile exercise to see whether or not sertindole falls within the rules and to ask why it is successful if it does not.
Thank you for your answer. Interresting read indeed. Could you maybe point me to a clue as to why a drug could still be succesfuld even when not "being in line"
Another thing I am wondering, is that due to the logD being relatively high would indicate that the drug is largely nonpolar at pH 7.4. Another thing I found with the assistance of a Bjerrum Plot at pH 7.4 the drug is positively charghed when a hydrogen atom becomes H+ ion. How is it that these two pieces of information is 'crucial' to the drug's effectioness?
I ask because with this topic I constantly feel like I am floating just above understanding it, and I hope that I will be able to land.