Developing inhaled drugs for respiratory diseases: A medicinal chemistry perspective.

Despite the devastating impact of many lung diseases on human health, there is still a significant unmet medical need in respiratory diseases, for which inhaled delivery represents a crucial strategy. More guidance on how to design and carry out multidisciplinary inhaled projects is needed. When designing inhaled drugs, the medicinal chemist must carefully balance the physicochemical properties of the molecule to achieve optimal target engagement in the lung. Although the medicinal chemistry strategy is unique for each project, and will change depending on multiple factors, such as the disease, target, systemic risk, delivery device, and formulation, general guidelines aiding inhaled drug design can be applied and are summarised in this review.

Recent advances in cancer therapeutics.

In the past 20 years, cancer therapeutics has undergone a paradigm shift away from the traditional cytotoxic drugs towards the targeting of proteins intimately involved in driving the cancer phenotype. The poster child for this alternative approach to the treatment of cancer is imatinib, a small-molecule kinase inhibitor designed to target chronic myeloid leukaemia driven by the BCR-ABL translocation in a defined patient population. The improvement in survival achieved by treatment of this patient cohort with imatinib is impressive. Thus, the aim is to provide efficacy but with low toxicity. The role of the medicinal chemist in oncology drug discovery is now closely aligned with the role in most other therapeutic areas with high-throughput and/or fragment-based screening, structure-based design, selectivity, pharmacokinetic optimisation and pharmacodynamic biomarker modulation, all playing a familiar part in the process. In this chapter, we selected four areas in which compounds are either approved drugs or in clinical trials. These are chaperone inhibitors, kinase inhibitors, histone deacetylase inhibitors and inhibitors of protein-protein interactions. Even within these areas, we have been selective, particularly for kinase inhibitors, and our aim has been to exemplify newer approaches and novel aspects of medicinal chemistry.