Alkanes and Cycloalkanes!

I didn't tell you the entire Enalapril story.  Enalaprilat was developed as an improvement over Captopril, the first oral ACE inhibitor used to treat hypertension. While Captopril’s thiol (–SH) group was effective for enzyme binding, it also caused significant adverse effects. To overcome this, medicinal chemists developed Enalaprilat, which replaced the thiol group with two carboxyl groups, reducing side effects. However, Enalaprilat had poor gastrointestinal absorption due to its highly polar nature, making it suitable only for intravenous use. To improve its bioavailability and enable oral administration, chemists modified Enalaprilat by adding a simple ethyl group, creating Enalapril. This modification transformed the drug's absorption profile, allowing it to be taken as a pill, which is more convenient and commercially viable.

Alkanes are generally not very water-soluble due to their nonpolar nature, which limits their ability to dissolve in the aqueous environment of the gastrointestinal (GI) tract. In the case of Enalapril, the addition of an ethyl group (a simple alkane chain) helped to balance its overall polarity, enhancing its ability to cross lipid-rich cell membranes and improving GI absorption, making the drug suitable for oral use.