Question 1) When comparing different compounds and their potential absorption from the intestines, the pKa and the pH values play an important role. Compare the following drugs with their given pKa values and estimate what percent you would expect to be unionized and therefore potentially absorbed into the body if pH = 4, 7, and 8 (three calculations for each compound). Furthermore describe or draw the structure in its ionized state (i.e. which functional group would be charged/ionized).
a) Salicylic acid (acidic pKa = 3.0)
b) Aniline (basic pKa = 4.6)
c) Quinine (basic pKa = 8.4)
Question 2) For salicylic acid and aniline from question 1, calculate the logP using the analytical approach described in the lesson notes. Provide the calculations with your submission. Then compare the calculated logP to the experimental logP obtained from the literature by looking up each compound on this website: Need Assignment Help?
Question 3) Read the following article which discusses the physicochemical properties of central nervous system (CNS) drugs on the market and compares them to drug candidates currently in development:
You do not need to understand all of the terms in detail but should get a general impression of the results obtained from this study. Answer the following questions in your own words:
Which parameters were significantly different between the marketed drugs and the drug candidates in the analysis? What do the authors conclude should be done about this difference?
Figure 6 in the article correlates ligand efficiency with ligand-lipophilicity efficiency. Explain these two terms in your own words and briefly state what the authors conclude from the comparison of marketed drugs and drug candidates.
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