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

Drug Development Research
Li ZhangGuiming Yang

Abstract

Preclinical Research 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.

References

Nov 9, 2005·Bioorganic & Medicinal Chemistry Letters·Wei DengFengming Chu
May 8, 2009·Journal of Medicinal Chemistry·Nobuaki SuzukiNaoki Miyata
Dec 25, 2009·Nature·Wenjun ZhouPasi A Jänne
Jan 1, 2009·Advances in Pharmacology·Khosrow Kashfi
Jul 17, 2010·Cardiovascular Therapeutics·Ruitang Deng, Te-Jin Chow
Apr 5, 2012·Nature Reviews. Clinical Oncology·Michael J ThunCarlo Patrono
Oct 15, 2013·European Journal of Medicinal Chemistry·Marc-Antoine BazinPascal Marchand
Jan 1, 2012·Pharmaceuticals·Melania DovizioPaola Patrignani
Dec 3, 2014·European Journal of Medicinal Chemistry·Hongping GaoJie Zhang

❮ Previous
Next ❯

Citations

May 16, 2020·International Journal of Molecular Sciences·Tereza KauerováPeter Kollar
Jul 3, 2021·Molecular Medicine Reports·Yuchen SunJian Liu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.