Scaffold Hopping in the drug discovery

Drug discovery and development process has been advancing with the help of modern concept based techniques aiming to achieve both intellectual property of interest and self-sufficient in vivo optimization. The importance of Intellectual property will be discussed in coming article and how it boosts the discovery phase effectively is must know concept from research viewpoint. However, drugs are small molecules that fit inside the body as it comprises of thousands of receptors and enzymes providing numerous binding sites, but, these small molecules have few serious problematic features in them. In general, a drug substance of natural origin, for say, compatible with specific dosage form that is administered into the body and subsequently follow ADME-T pathway. Now, the ADME-T profile of any drug is important to decide whether the purpose is served or not, meaning, if it is showing specific action effectively. It has been seen that structural modification of these natural product derived drugs is detrimental for optimization in terms of activity and association with the target. 

Fig. General Scaffold hopping design

Natural products are often analyzed hoping to get the exact molecular framework along with the correct stereochemistry in the synthesized molecules. But, it is not always possible to achieve it, so, researchers do QSAR study to understand the biological relevance in terms of single atom or a group of atoms present in the molecule. This strategy became successful and they started to navigate into those pharmacophores, a portion of the molecule resoponsible for pharmacological activity, applying differenct concepts such as molecular similarity, bioisosterism and structure based design. 

Scaffold Hopping is such kind of programme which utilize all these aforementioned concepts. The moment it has been explored from both industry and research viewpoint, huge leap is taken in drug discovery process with increasing interest in patenting intellectual property of interest such as novel molecules and synthetic routes as well. And this effort has provided enthusiasm to the researchers to explore and find novel targets as well enhancing pharmacokinetic and pharmacodynamic profiling of the natural product derived novel scaffolds with same but improved pharmacological activity.