Medicinal Chemistry 3

The hydroxyethylamine moiety mimics the transition state for the catalytic reaction, but it is stable to the reaction. A bioisostere is a moiety that can be used in place of another group, whilst retaining the desired pharmaceutical activity.

Chloramphenicol is one of the most toxic antibacterial agents in clinical use, and should be reserved for life-threatening infections.

There is no electron-withdrawing group, and so the penicillin is acid sensitive. As a result, it cannot be taken orally. The presence of the steric shields also makes it more difficult for the penicillin to attack the transpeptidase enzyme. This means that methicillin has a lower activity and a narrower spectrum of activity compared to penicillin G.

Aspartic acid 25 and 25′ are involved in the catalytic mechanism which hydrolyses the peptide bond of a protein substrate.

Structure A is aciclovir and is phosphorylated in virally infected cells to its active triphosphate form. Structure B is valaciclovir which is the valine prodrug of aciclovir. It is converted to aciclovir by enzymes in the liver. Structure C is desciclovir which is metabolised by cellular xanthine oxidase to give aciclovir. Gangciclovir is not converted to acyclovir, and so cannot generate aciclovir triphosphate.

The two main targets currently used in anti-HIV therapy are reverse transcriptase and protease. However, integrase and the viral glycoproteins gp120 and gp41 are newer, alternative targets for anti-HIV therapy.