Drug Optimization (Lead Optimization?)

Pharmaceutical Companies are trying to fill their drug portfolio by optimizing the marketed drugs. Most of the recently launched drugs that are structurally similar to already known drugs, with only minor differences.The most common drug optimization methods are:


1. Reactive metabolites

A good example of this is venlafaxine (Effexor) and desvenlafaxine ( Pristiq). Desvenlafaxine is the metabolite of venlafaxine. The difference is that desvenlafaxine having O-H instead of O-Me.

2. Switching a Hydrogen atom with heavier isotopes

Pharma companies hopes that the deuterated drug survives longer in the body and fewer side effects, because the Deuterium can make stronger chemical bond than Hydrogen.

3. Racemic switching

Racemic switching is the redevelopment in a single enantiomer from a drug that was fist approved as a racimate, a better example is the Nexium. It is a predecessor Prilosec, a mixture of both S and R isomers. When Prilosec’s patent expired in 2001, the drug maker was ready with Nexium, which contains only the S-isomer.

The proliferation of "me-too" drugs leads to beneficial cost reductions.
But in the end, the real question is about pharmaceutical innovation. While “me too” fill the development pipeline; the creativity is fading away in the Art of Drug Discovery.