Optimization of gefitinib analogues with potent anticancer activity

Kai Hao Yin; Yi Han Hsieh; Rohidas S. Sulake; Su Pei Wang; Jui-I Chao; Chinpiao Chen

doi:10.1016/j.bmcl.2014.09.056

Optimization of gefitinib analogues with potent anticancer activity

Kai Hao Yin, Yi Han Hsieh, Rohidas S. Sulake, Su Pei Wang, Jui-I Chao^*, Chinpiao Chen

^*Corresponding author for this work

Institute of Molecular Medicine and Bioengineering

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

The interactions of gefitinib (Iressa) in EGFR are hydrogen bonding and van der Waals forces through quinazoline and aniline rings. However the morpholino group of gefitinib is poorly ordered due to its weak electron density. A series of novel piperazino analogues of gefitinib where morpholino group substituted with various piperazino groups were designed and synthesized. Most of them indicated significant anti-cancer activities against human cancer cell lines. In particular, compounds 52-54 showed excellent potency against cancer cells. Convergent synthetic approach has been developed for the synthesis of gefitinib intermediate which can lead to gefitinib as well as numerous analogues.

Original language	English
Pages (from-to)	5247-5250
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2014.09.056
State	Published - 15 Nov 2014

Keywords

A549
Anti-cancer
EGFR
Gefitinib
Iressa

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2014.09.056

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title = "Optimization of gefitinib analogues with potent anticancer activity",

abstract = "The interactions of gefitinib (Iressa) in EGFR are hydrogen bonding and van der Waals forces through quinazoline and aniline rings. However the morpholino group of gefitinib is poorly ordered due to its weak electron density. A series of novel piperazino analogues of gefitinib where morpholino group substituted with various piperazino groups were designed and synthesized. Most of them indicated significant anti-cancer activities against human cancer cell lines. In particular, compounds 52-54 showed excellent potency against cancer cells. Convergent synthetic approach has been developed for the synthesis of gefitinib intermediate which can lead to gefitinib as well as numerous analogues.",

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AU - Sulake, Rohidas S.

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AU - Chao, Jui-I

AU - Chen, Chinpiao

PY - 2014/11/15

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AB - The interactions of gefitinib (Iressa) in EGFR are hydrogen bonding and van der Waals forces through quinazoline and aniline rings. However the morpholino group of gefitinib is poorly ordered due to its weak electron density. A series of novel piperazino analogues of gefitinib where morpholino group substituted with various piperazino groups were designed and synthesized. Most of them indicated significant anti-cancer activities against human cancer cell lines. In particular, compounds 52-54 showed excellent potency against cancer cells. Convergent synthetic approach has been developed for the synthesis of gefitinib intermediate which can lead to gefitinib as well as numerous analogues.

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Optimization of gefitinib analogues with potent anticancer activity

Abstract

Keywords

UN SDGs

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