Strained ladderane cages step in for flat ortho-benzene rings in known drugs
- Experimental follow-up to an earlier hypothesis: ladderane cores can stand in for ortho-substituted benzene rings in bioactive molecules.
- Disubstituted ladderane building blocks were prepared efficiently and characterized in depth, then swapped into several known bioactive compounds in place of the aromatic ring.
- Ladderane analogues of Thalidomide and Oxatomide, free of existing patent coverage, showed better physicochemical properties while keeping comparable biological activity.
- This is an unreviewed chemRxiv preprint.
💡 Points Based on the abstract
Does the cage truly reproduce the ortho exit vectors, or only the silhouette? Matching activity in two known drugs is encouraging, but the chiral, strained core worries me: stereochemistry, and stability under metabolic and acidic conditions. The patent-free angle is the selling point, provided the building blocks scale beyond a one-off route.