In the study titled "Design, Synthesis, and Structure–Activity Relationship Studies of 6H-benzo[b]indeno[1,2-d]thiophen-6-one Derivatives as DYRK1A/CLK1/CLK4/Haspin Inhibitors," Lomberget and colleagues have crafted a new symphonic piece in the realm of medicinal chemistry. They present a novel class of DYRK1A/CLK1/CLK4/Haspin inhibitors based on the tetracyclic benzo[b]indeno[1,2-d]thiophen-6-one scaffold.
The study exemplifies a standard medicinal chemistry strategy for drug discovery by integrating synthetic chemistry, biological assessment, and computational techniques to develop and elucidate potential new kinase inhibitors. The study is anticipated to capture the interest of readers of RSC Medicinal Chemistry. However, some minor issues need to be addressed before the manuscript can be published.
- Table 1, which presents the yields obtained for the synthesis of keto derivatives 6 and tetracyclic compounds 4, could be moved to the supporting materials or considered for deletion. This is particularly advisable since the content is already detailed in the experimental section.
- I believe the presentation of the schemes could be improved. If the authors are open to modifications, I suggest merging Schemes 2 and 3, which detail the synthesis of iodobenzaldehydes, into a single scheme. Additionally, Schemes 1, 4, and 5 could be combined into one or two cohesive schemes for better clarity and flow.
- The findings in Table 2 are the most important in this study and should be presented more effectively.
- There are many typos and language mistakes in the manuscript, so please revise it thoroughly. The following are just a few examples.
A series of four-membered sulfur-containing heterocycles
with higher half-life -----> with a higher half-life
Since the approval of Imatinib in 2001 and clinical successes -----> and the clinical successes
tetracylic derivative -----> tetracyclic derivative
itself obtained -----> which was itself obtained
2-iodo benzyl alcohol -----> 2-iodobenzyl alcohol
As expected, 4k also inhibits strongly -----> As expected, 4k also strongly inhibits

The manuscript has been improved.