Abstract
A library of 34 lipophilic sulfonamides based upon the memantine core has been synthesized to identify potential drug candidates to cross the blood-brain barrier and target glioblastoma. The library was screened for in vitro activity against 4 mammalian cell lines, including U-87 (glioblastoma). Additional synthetic variation of the active compounds has validated the importance of specific regions of the pharmacophore, with the sulfonamide functionality and S-aryl unit displaying the most significant impact. In silico investigations suggest the active compounds might target DDR1 or RET proteins. The investigation has resulted in several compounds that warrant further development for lead optimization.
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