Design, synthesis, and biological evaluation of novel 3-pyrrolo[b] cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors

Lei Ding; Feng Tang; Wei Huang; Qiu Jin; Han Shen; Ping Wei

doi:10.1016/j.bmcl.2013.08.037

Design, synthesis, and biological evaluation of novel 3-pyrrolo[b] cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors

Lei Ding, Feng Tang, Wei Huang, Qiu Jin, Han Shen, Ping Wei

COLLEGE OF BIOTECHNOLOGY AND PHARMACEUTICAL ENGINEERING

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

17 Scopus citations

Abstract

A novel series of 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives targeting VEGFR-2, PDGFR-β and c-Kit kinases were designed and synthesized. The molecular design was based on the SAR features of indolin-2-ones as kinase inhibitors. SAR study of the series allowed us to identify compounds possessing more potent inhibitory activities against the three kinases than sunitinb with IC₅₀ values in the low nanomolar range in vitro. Additionally, some compounds also showed favorable antiproliferative activities against a panel of cancer cell lines (BXPC-3, T24, BGC, HEPG2 and HT29).

Original language	English
Pages (from-to)	5630-5633
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	20
DOIs	https://doi.org/10.1016/j.bmcl.2013.08.037
State	Published - 15 Oct 2013

Keywords

2-Dihydroindolinone derivatives
Antiproliferative
Inhibitor
Molecular docking
Receptor tyrosine kinase

UN SDGs

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

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10.1016/j.bmcl.2013.08.037

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title = "Design, synthesis, and biological evaluation of novel 3-pyrrolo[b] cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors",

abstract = "A novel series of 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives targeting VEGFR-2, PDGFR-β and c-Kit kinases were designed and synthesized. The molecular design was based on the SAR features of indolin-2-ones as kinase inhibitors. SAR study of the series allowed us to identify compounds possessing more potent inhibitory activities against the three kinases than sunitinb with IC50 values in the low nanomolar range in vitro. Additionally, some compounds also showed favorable antiproliferative activities against a panel of cancer cell lines (BXPC-3, T24, BGC, HEPG2 and HT29).",

keywords = "2-Dihydroindolinone derivatives, Antiproliferative, Inhibitor, Molecular docking, Receptor tyrosine kinase",

author = "Lei Ding and Feng Tang and Wei Huang and Qiu Jin and Han Shen and Ping Wei",

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T1 - Design, synthesis, and biological evaluation of novel 3-pyrrolo[b] cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors

AU - Ding, Lei

AU - Tang, Feng

AU - Huang, Wei

AU - Jin, Qiu

AU - Shen, Han

AU - Wei, Ping

PY - 2013/10/15

Y1 - 2013/10/15

N2 - A novel series of 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives targeting VEGFR-2, PDGFR-β and c-Kit kinases were designed and synthesized. The molecular design was based on the SAR features of indolin-2-ones as kinase inhibitors. SAR study of the series allowed us to identify compounds possessing more potent inhibitory activities against the three kinases than sunitinb with IC50 values in the low nanomolar range in vitro. Additionally, some compounds also showed favorable antiproliferative activities against a panel of cancer cell lines (BXPC-3, T24, BGC, HEPG2 and HT29).

AB - A novel series of 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives targeting VEGFR-2, PDGFR-β and c-Kit kinases were designed and synthesized. The molecular design was based on the SAR features of indolin-2-ones as kinase inhibitors. SAR study of the series allowed us to identify compounds possessing more potent inhibitory activities against the three kinases than sunitinb with IC50 values in the low nanomolar range in vitro. Additionally, some compounds also showed favorable antiproliferative activities against a panel of cancer cell lines (BXPC-3, T24, BGC, HEPG2 and HT29).

KW - 2-Dihydroindolinone derivatives

KW - Antiproliferative

KW - Inhibitor

KW - Molecular docking

KW - Receptor tyrosine kinase

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M3 - 文章

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JO - Bioorganic and Medicinal Chemistry Letters

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Design, synthesis, and biological evaluation of novel 3-pyrrolo[b] cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors

Abstract

Keywords

UN SDGs

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