The synthesis and tubulin binding activity of thiophene-based analogues ofcombretastatin A-4

A number of analogues of combretastatin A-4 (1), containing a thiophene rin g interposed between the two phenyl groups, have been prepared. The synthes is of these compounds employed. a combination of palladium-mediated couplin g and iodocyclization techniques. The thiophene compounds 11, 14, 18, and 1 9 also represent non-benzofused analogues of some recently described tubuli n binding benzo[b]thiophenes 3 5. The most active thiophene compounds ident ified in this study were 11, 14, and 18. Overall they are less active than I but exhibit comparable activity to the most active of the benzo[b]thiophe nes 3 5. A structure-activity relationship or these compounds is considered . (C) 2001 Elsevier Science Ltd. All rights reserved.