Problem 2 Below are listed some of the top selling drugs along with their clogP
ID: 63040 • Letter: P
Question
Problem 2 Below are listed some of the top selling drugs along with their clogP and polar surface area (PSA) values. activity cLogP PSA esomeprazole Anti-acid reflux 2.56 72.6 rosuvastatin anticholesterol 0.93 148.7 atorvastatin anticholesterol 4.45 110.0 quetiapine Antipsychotic (CNS) 2.99 48.2 aripiprazole Antidepressant (CNS) 5.31 44.8 duloxetine Antidepressant (CNS) 4.25 21.2 AMS-167 38.7 SCP-123 132.8 Briefly explain the following: a) Based on the activity above how does the PSA relate to BBB penetration? b) Would you expect AMS-167 or SCP123 to be CNS active compounds?
Explanation / Answer
a. PSA relates to the prediction of the drug transporting properties. It is defined as a sum of surfaces of polar atoms (usually oxygens, nitrogens and attached hydrogens) in a molecule. This parameter has been shown to correlate very well with the human intestinal absorption, Caco-2 monolayers permeability, and blood-brain barrier penetration.
The PSA values of over 140 angstroms are considered as poor permeating compounds.
b. Molecules which are less than 90 angstroms are considered as good permeating compounds with respect to the blood-brain barrier. So among the two compounds AMS-167 could be CNS-active compound due to its relatively low PSA value of 38.7 compared to SCP123
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