Synthesis of p‐O‐Alkyl Salicylanilide Derivatives as Novel EGFR Inhibitors

ABSTRACT

Epidermal growth factor receptor (EGFR), a validated target for anticancer drugs, plays a critical role in tumorigenesis and tumor development. A series of p‐O‐alkyl salicylanilide derivatives were designed and synthesized as novel EGFR inhibitors using a salicylic acid scaffold. A simulated six‐membered ring strategy formed through intramolecular hydrogen bonds was employed to mimic the planar quinazoline of the EGFR antagonist, gefitinib. The derived compounds with hydroxyl at the ortho position were more potent than ones with methoxyl group. In particular, compounds 5d and 5b displayed significant EGFR inhibitory (IC50 values = 0.30 and 0.45 μM, respectively) activity as well as potent antiproliferative activity in A431 and HCT‐116 tumor cells. These salicylanilides could be considered as promising lead compounds for developing novel EGFR inhibitors. Drug Dev Res, 2016. © 2016 Wiley Periodicals, Inc.

Source: Drug Development Research - January 13, 2016 Category: Drugs & Pharmacology Authors: Li Zhang, Lin Hou, Wenyan Sun, Zidong Yu, Jibo Wang, Hua Gao, Guiming Yang Tags: Research Article Source Type: research