二芳基脲：抗癌剂的专用结构

Title:Diaryl Urea: A Privileged Structure in Anticancer Agents

Volume: 23 Issue: 15

Author(s): Laura Garuti, Marinella Roberti, Giovanni Bottegoni, Mariarosaria Ferraro

Affiliation:

关键词: 二芳基脲；抗癌活性；DNA烷化剂；SAR；DFG-out;激酶抑制剂;杂环化合物。

摘要: The diaryl urea is an important fragment/pharmacophore in constructing anticancer molecules due to its near-perfect binding with certain acceptors. The urea NH moiety is a favorable hydrogen bond donor, while the urea oxygen atom is regarded as an excellent acceptor. Many novel compounds have been synthesized and evaluated for their antitumor activity with the successful development of sorafenib. Moreover, this structure is used to link alkylating pharmacophores with high affinity DNA binders. In addition, the diaryl urea is present in several kinase inhibitors, such as RAF, KDR and Aurora kinases. Above all, this moiety is used in the type II inhibitors: it usually forms one or two hydrogen bonds with a conserved glutamic acid and one with the backbone amide of the aspartic acid in the DFG motif. In addition, some diaryl urea derivatives act as Hedgehog (Hh) ligands, binding and inhibiting proteins involved in the homonymous Hh signaling pathway. In this review we provide some of the methodologies adopted for the synthesis of diaryl ureas and a description of the most representative antitumor agents bearing the diaryl urea moiety, focusing on their mechanisms bound to the receptors and structure-activity relationships (SAR). An increased knowledge of these derivatives could prompt the search to find new and more potent compounds.

Cite this article as:

Laura Garuti, Marinella Roberti, Giovanni Bottegoni, Mariarosaria Ferraro , Diaryl Urea: A Privileged Structure in Anticancer Agents, Current Medicinal Chemistry 2016; 23 (15) . https://dx.doi.org/10.2174/0929867323666160411142532