CGP 52411 is an inhibitor of the enzyme protein kinase. It acts on the kinase-active site of the EGFR (Epidermal Growth Factor Receptor). Analysis of its structure-activity relationships indicate that certain substituent on the chromatic rings (chlorine, methyl or hydroxyl groups) hinder the drug activity.
The drug gets metabolized due to para-hydroxylation, which generates inactive metabolites. It is important to protect the drug from the metabolism, so that it reaches its target.
Para-hydroxylation of the drug CGP 52411 means that a hydroxyl group is added to the fourth carbon atom in the benzene ring. Addition of the hydroxyl group renders the drug CGP 52411 inactive.
The drug is fast metabolized by enzymes like cytochrome P450. It has been found that addition of a chlorine group or a methyl group or a hydroxyl group to improve the drug activity and slow down its fast metabolism is ineffective.
Addition of a fluorine (F) group is known to stabilize the drug molecule and block para-hydroxylation. This happens because F binds strongly to the carbon atom and imparts polarity to the drug. Fluorine based drugs have a longer shelf-lives.
However, addition of a similar molecule, chlorine (C) does not prevent the para-hydroxylation reaction. This is because chlorine is a much larger atom and binds loosely with carbon. Addition of a hydroxyl group will directly lead to drug inactivation.