Design and combinatorial synthesis of a library of methylenesulfonamides and related compounds as potential kinase inhibitors.
An effective parallel solid phase route to methylenesulfonamides and amides bearing a wide variety of substituents is described. The three key reaction steps were reductive amination of a haloheteroaromatic aldehyde onto a benzhydrylamine type polystyrene resin, sulfonamide or amide formation and palladium catalysed transformation of the remaining heteroaromatic halogen. A process of virtual library design and filtering, together with solution and solid phase optimizations, aided the preparation of several novel drug-like product classes in high purities and should allow access to a variety of further useful analogues.
Torr
Jane E
JE
Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Surrey SM25NG, UK.
Large
Jonathan M
JM
McDonald
Edward
E
D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D008698:Mesylates / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000138:chemical synthesis; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology
D008698:Mesylates; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D013449:Sulfonamides