Submission Details
Molecule(s):
NS(=O)(=O)c1cc2c(cc1Cl)NCN(CCC(=O)Nc1cccnc1)S2(=O)=O
Design Rationale:
Analysing the non-covalent fragments I see two main hotspots: one is a benzenesulfonamide and the other is a pyridine. This made me immediately think of benzenesulfonamide drugs as there are a few of those. Among them, Hydrochlorothiazide seems to both nicely fulfil the benzensulfonamide pharmacophore as the N of the secondary sulfonamide also so-localizes with the tertiary amine of a few other fragments (e.g. x0354). So, on the one side, you could potentially cocrystalize Hydrochlorothiazide alone and explore it for repurposing. On the other hand, as the compound is commercial, you could use it as a scaffold. I have used it as a scaffold in the molecule I sketched and explored whether I could add a pyridine with a linker to reach the pyridine hotspot. I think the linker I used would be the ideal length but you could explore several other linkers as well. I believe it should be possible to derivatize the sulfonamide but it's true that this could be challenging given there is another sulfonamide in the structure that could cross-react. I hope this helps, thank you so much for this initiative!