1,4-DHP can modulate the L-type calcium channels, the DHP ring has 3,5 ester substituents and 2,6 methyl group(most common). If these positions (3 and 5) or (2 and 6) have different substituents the compound will be chiral. The activity of one enantiomer may be more active than the other in many cases but do they have different action on the receptor?
Firstly it could not be surely said that the compound after the modifications you have mentioned will bind into that particular receptor where 1,4 DHP binds. Secondly, the presence of chiral centre in a molecule do play an important role in its binding to the desired receptor due to its chiral recognition ability. Accordingly it is possible that one stereoisomer could be healthy for a particular activity while the another one may or may not be unhealthy. Since body contains diverse array receptors the undesired stereoisomer could interfere with any of those. The best example of a chiral drug gone wrong is THALIDOMIDE.
Firstly, according to SAR for DHP, these modifications do not abolish activity and are allowed. Secondly depending on the nature of substitution (Polar/nonpolar), if same nature the stereoisomer will have the same type of activity; if opposite nature the stereoisomer will be agonist and antagonist activity relationship.(have different type of activity)
Yes, this could happen. For example, (-)-BAY K 8644 is a L-type Ca2+ Activator DHP. It's enantiomer, (+)-Bay K 8644, is an antagonist.
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