Synthesis of a 3-(伪-Styryl)benzo[b]-thiophene Library via Bromocyclization of Alkynes and Palladium-Catalyzed Tosylhydrazones Cross-Couplings: Evaluation as Antitubulin Agents
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- 作者：Bret Tr茅guier ; Marie Lawson ; Guillaume Bernadat ; J茅r么me Bignon ; Jo毛lle Dubois ; Jean-Daniel Brion ; Mouad Alami ; Abdallah Hamze
- 刊名：ACS Combinatorial Science
- 出版年：2014
- 出版时间：December 8, 2014
- 年：2014
- 卷：16
- 期：12
- 页码：702-710
- 全文大小：579K
- ISSN：2156-8944
文摘
A library of functionalized 3-(伪-styryl)-benzo[b]thiophenes, endowed with a high level of molecular diversity, was efficiently synthesized by applying a synthetic sequence that allowed introduction of various substituents on aromatic A, B, and C-rings. The strategy developed involves the synthesis of 3-bromobenzo[b]thiophene derivatives through a bromocyclization step of methylthio-containing alkynes using N-methylpyrrolidin-2-one hydrotribromide reagent (MPHT). Further coupling of 3-bromobenzothiophenes under palladium-catalysis with N-tosylhydrazones efficiently furnished 2-aryl-3-(伪-styryl)benzo[b]thiophene derivatives. The antiproliferative properties of target compounds were studied. Among them, compound 5m has demonstrated submicromolar cytotoxic activity against HCT-116 cell line, and inhibited the polymerization of tubulin at micromolar level comparable to that of CA-4.