The strategic incorporation of chloro and methoxy groups in small molecule design is gaining prominence in drug discovery, influencing both intermolecular interactions and overall drug efficacy. Recent studies underscore the beneficial effects of these substituents, highlighting their impact on target binding and pharmacokinetic properties.
Yoshihiro Ishihara's presentation on the roles of chloro and methoxy groups emphasized their ability to enhance intermolecular interactions. This enhancement can lead to improved binding affinity and selectivity for drug targets. The unique advantages and disadvantages of employing these substituents were also discussed, providing a nuanced perspective on their application in medicinal chemistry.
Several high-profile clinical readouts have featured small molecules incorporating chloro and methoxy groups. These include molecules targeting Bruton's tyrosine kinase (BTK) for multiple sclerosis (MS), as well as Axl, TYRO3, and Mer kinases for oncology applications. Additionally, inhibitors targeting HIF prolyl-hydroxylase in anemia, ET/AT in nephrology, a JAK2 inhibitor for myelofibrosis, and THR-beta in NASH have demonstrated the importance of these functional groups.
The strategic use of chloro and methoxy groups allows medicinal chemists to fine-tune drug properties, optimizing for both efficacy and safety. By understanding the specific contributions of these functional groups, researchers can design more effective and targeted therapies.
