Dedicated to our co-founder Prof. Erick Carreira
Abstract
Target-first drug discovery relies heavily on protein structure information, which severely limits its application. In recent years, fragment-based drug Design (FBDD) has been identified as an alternative solution, where screening of smaller molecules for lower affinity allowed the use of focused libraries with a higher hit rate. It is shown that coupling an sp2-rich heteroaromatic group with a monofunctional sp3-rich core gives fragments (186 examples) with advantageous physical-chemical properties, covering a chemical space often neglected in traditional libraries.
Key words
fragment-based drug design - azetidine - oxetane - medicinal chemistry - aqueous solubility - logP
