Construction of benzofuranone library via a metal-free, one-pot intermolecular condensation, and their application as efficient estrogen receptor β modulators

• Published in: Chemical communications (Cambridge, England) Vol. 55; no. 97; pp. 14570 - 14573
• Main Authors: Peng, Xueke, Hu, Zhiye, Zhang, Jing, Ning, Wentao, Zhang, Silong, Dong, Chune, Shi, Xiaodong, Zhou, Hai-Bing
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 18.12.2019
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Aromatic compounds; Benzofurans - chemical synthesis; Benzofurans - chemistry; Benzofurans - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Crystallography; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Estrogen Receptor alpha - antagonists & inhibitors; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - agonists; Estrogen Receptor beta - metabolism; Estrogen Receptor Modulators - chemical synthesis; Estrogen Receptor Modulators - chemistry; Estrogen Receptor Modulators - pharmacology; Estrogens; Humans; Ketones; Models, Molecular; Modulators; Molecular Structure; Receptors; Selectivity; Structure-Activity Relationship
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/c9cc05756k

Facile synthesis of benzofuranone was achieved through a metal-free, one-pot intermolecular condensation between α-hydroxy aryl ketones and resorcinol derivatives. A library of 20 compounds with moderate to good overall yields was prepared. These compounds showed strong binding toward estrogen receptors along with good selectivity for ERβ (>190-fold over ERα). Anti-proliferative activity on DU-145, U-87, and MCF-7 cells gave inhibition IC values in the low μM range, which suggested the promising potential therapeutic applications of these new classes of benzofuranones.