Ring Transformations

New Pyrrole Derivatives with Potent Tubulin Polymerization Inhibiting Activity As Anticancer Agents Including Hedgehog-Dependent Cancer

“…Compounds 4, 10−20, 32−41, 45, 47−55, and 56−60 were prepared by microwave (MW)-assisted reaction of the appropriate 1-substituted pyrrole with 3,4,5-trimethoxybenzoyl chloride in the presence of anhydrous aluminum chloride in (11) did not inhibit tubulin assembly, emphasizing the essential role of these moieties for the antitubulin activity of ARAPs. Introduction of either a chlorine or fluorine atom on the 1-phenyl ring yielded potent tubulin polymerization inhibitors (compounds 12−17).…”

“…11 This strategy allowed us to explore the potential of 3-aroyl-1-arylpyrrole (ARAP) derivatives as inhibitors of tubulin polymerization. In recent years, other groups have reported the discovery of tubulin binding agents sharing structural similarities to ARAPs.…”

“…10 Splitting of fused rings by following a disjunctive approach often yields new biologically active chemical entities that show the same mechanism of action, weaker cytotoxicity, and improved pharmacokinetic properties. 11 This strategy allowed us to explore the potential of 3-aroyl-1-arylpyrrole (ARAP) derivatives as inhibitors of tubulin polymerization. In recent years, other groups have reported the discovery of tubulin binding agents sharing structural similarities to ARAPs.…”