Question
I am in an online drug design class and I need a some guidance.
CHEM 5332A LogP Classwork. Name Due Thursday at 11:30pm Answer the following questions and save as M3-LogPSu17YourName.doc. Try your best to show your work. Return to the assignment area where you found the document and submit (upload) to the assignment area. Lipophilicity is an important factor for drug activity, and the quantitative measure of lipophilicity benefits drug development. Hansch devised a simple methodology to measure the correlation between lipid solubility and biological activity. Step 1: The solubility of the compound in 1-octan relative to H2O. (1-Octanol ol simulates a natural lipid membrane.) To measure the solubility, we use a partition coefficient, P, between 1-octanol and H20. [compound]oct [compound loct [compound Jag (-a) compound)aq degree of dissociation of the compound in water calculated from ionization Constants Compounds are mixed in varying ratios of 1-octanol and H20, and the concentration of the compound in each layer is determined. The rate of movement of drugs through cell membranes is approximately proportional to the logarithm of their partition coefficients. Pk1: drug is more soluble in H2O than in 1-octanol P 1: drug is more soluble in 1-octanol than in H20 The larger the logP the more lipophilic the drug is. In general, logP should be below 5 to be effective. Dosing Form Injectable Oral
Explanation / Answer
1. As logP increases,
Aqueous solubility decreases
Absorption through cell membrane increases
binding to polar enzymes decreases
absorption in the stomach increases
2. with logP = -1.4
solubility in octanol,
-1.4 = log(x/0.24)
solubility in octanol = 7.37 M
3. solubility
logP = log(2.05/0.145)
= 1.15
4. Lipinski's rule
a) violation of no more than one rule among,
More than 5 hydrogen bond donors
A more than 10 hydrogen bond acceptors
A molecular mass greater than 500 amu
A log P greater than 5
b) Log P is lower than 5, so it would be an effective drug and according to the rules described above.
