Design, Palladium-Catalyzed Synthesis, and Biological Investigation of 2-Substituted 3-Aroylquinolin-4(1H)-ones as Inhibitors of the Hedgehog Signaling Pathway

被引：29

作者：

Alfonsi, Romina ^{[1
]}

Botta, Bruno ^{[2
]}

Cacchi, Sandro ^{[2
]}

Di Marcotullio, Lucia ^{[1
,4
]}

Fabrizi, Giancarlo ^{[2
]}

Faedda, Roberta ^{[1
]}

Goggiamani, Antonella ^{[2
]}

Iazzetti, Antonia ^{[2
]}

Mori, Mattia ^{[3
]}

机构：

[1] Sapienza Univ, Dept Mol Med, Viale Regina Elena 291, I-00161 Rome, Italy

[2] Sapienza Univ, Dipartimento Chim & Tecnol Farmaco, Piazzale A Moro 5, I-00185 Rome, Italy

[3] Ctr Life Nano Sci Sapienza, Ist Italiano Tecnol, Viale Regina Elena 291, I-00161 Rome, Italy

[4] Sapienza Univ, Fdn Cenci Bolognetti, Ist Pasteur, Viale Regina Elena 291, I-00161 Rome, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 60卷 / 04期

关键词：

STEM-CELLS; DEPENDENT TUMORS; MEDULLOBLASTOMA; CYCLOPAMINE; PROGENITORS; GROWTH; CANCER; GLI;

D O I：

10.1021/acs.jmedchem.6b01135

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

2-Substituted 3-aroylquinolin-4(1H)-ones, prepared through a palladium-catalyzed carbonylative cyclization of N-(2-iodoaryl)enaminones, proved to inhibit efficiently the Hedgehog pathway through direct antagonism of the wild-type and drug-resistant form of the Smoothened receptor. Notably, these compounds repressed the Hh-dependent growth events and the proliferation of tumor cells with aberrant activation of the Hh pathway, which plays a crucial role in development and tumorigenesis.

引用

页码：1469 / 1477

页数：9

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