Diaryl Urea: A Privileged Structure in Anticancer Agents
| Autor: | Giovanni Bottegoni, Marinella Roberti, Laura Garuti, Mariarosaria Ferraro |
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| Přispěvatelé: | Garuti, Laura, Roberti, Marinella, Ferraro, Mariarosaria, Bottegoni, Giovanni |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Stereochemistry Diaryl urea Antineoplastic Agents 01 natural sciences Biochemistry 03 medical and health sciences chemistry.chemical_compound anticancer activity DNA-alkylating agents SAR DFG-out kinase inhibitors heterocycles Neoplasms Amide Drug Discovery Aspartic acid Animals Humans Urea Moiety Hedgehog Proteins Diaryl urea anticancer activity DNA-alkylating agents SAR DFG-out kinase inhibitors heterocycles Pharmacology 010405 organic chemistry Chemistry Hydrogen bond Organic Chemistry Glutamic acid 0104 chemical sciences 030104 developmental biology Molecular Medicine Pharmacophore DNA |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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