Discovery of anilino-furo[2,3- d ]pyrimidine derivatives as dual inhibitors of EGFR/HER2 tyrosine kinase and their anticancer activity

Hossam, Monia; Lasheen, Deena S.; Ismail, Nasser S. M.; Esmat, Ahmed; Mansour, Ahmed M.; Singab, Abdel Nasser B.; Abouzid, Khaled A. M.

doi:10.1016/j.ejmech.2017.12.022

Cited by 32 publications

(13 citation statements)

References 43 publications

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“…These compounds were capable of showing a weak dual inhibitory activity toward EGFR and ErbB2. Also, the antiproliferative studies proved that the compounds exhibited a significant loss of activity ( Hossam et al, 2018 ).…”

Section: Fused Pyrimidine Derivativesmentioning

confidence: 99%

“… 4) At R 3 : methyl substituents were found to be active ( Devambatla et al, 2018 ). The carboxylate derivatives showed a significant loss of activity ( Hossam et al, 2018 ). The presence of a phenyl ring decreases anticancer activity ( Lin et al, 2019 ).…”

Section: Fused Pyrimidine Derivativesmentioning

confidence: 99%

“…Fusing with benzene slightly reduces its activity ( Showalter et al, 1999 ). Replacing with the methyl group significantly decreases the inhibitory activity ( Hossam et al, 2018 ; Lin et al, 2019 ).…”

Section: Fused Pyrimidine Derivativesmentioning

confidence: 99%

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A Review on Fused Pyrimidine Systems as EGFR Inhibitors and Their Structure–Activity Relationship

et al. 2022

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Epidermal growth factor receptor (EGFR) belongs to the family of tyrosine kinase that is activated when a specific ligand binds to it. The EGFR plays a vital role in the cellular proliferation process, differentiation, and apoptosis. In the case of cancer, EGFR undergoes uncontrolled auto-phosphorylation that results in increased cellular proliferation and decreased apoptosis, causing cancer promotion. From the literature, it shows that pyrimidine is one of the most commonly studied heterocycles for its antiproliferative activity against EGFR inhibition. The authors have collated some interesting results in the heterocycle-fused pyrimidines that have been studied using different cell lines (sensitive and mutational) and in animal models to determine their activity and potency. It is quite clear that the fused systems are highly effective in inhibiting EGFR activity in cancer cells. Therefore, the structure–activity relationship (SAR) comes into play in determining the nature of the heterocycle and the substituents that are responsible for the increased activity and toxicity. Understanding the SAR of heterocycle-fused pyrimidines will help in getting a better overview of the molecules concerning their activity and potency profile as future EGFR inhibitors.

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Section: Fused Pyrimidine Derivativesmentioning

confidence: 99%

Section: Fused Pyrimidine Derivativesmentioning

confidence: 99%

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A Review on Fused Pyrimidine Systems as EGFR Inhibitors and Their Structure–Activity Relationship

et al. 2022

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“…Dual EGFR/HER2 Inhibitors Bearing a Furo[2,3d]pyrimidine Scaffold. Hossam et al 63 identified the bioisotere furo [2,3-d]pyrimidine as the parent nucleus and introduced the aniline part at the 4-position of gefitinib and lapatinib. The replacement of the original aromatic group at the 5-position, with a large hindrance, into the side chain with relatively low lipophilicity provides more interaction with the solvent assessable region.…”

Section: Egfr Dual-target Inhibitors and Othermentioning

confidence: 99%

Development of Dual Inhibitors Targeting Epidermal Growth Factor Receptor in Cancer Therapy

et al. 2022

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Epidermal growth factor receptor (EGFR) is of great significance in mediating cell signaling transduction and tumor behaviors. Currently, third-generation inhibitors of EGFR, especially osimertinib, are at the clinical frontier for the treatment of EGFR-mutant non-small-cell lung cancer (NSCLC). Regrettably, the rapidly developing drug resistance caused by EGFR mutations and the compensatory mechanism have largely limited their clinical efficacy. Given the synergistic effect between EGFR and other compensatory targets during tumorigenesis and tumor development, EGFR dual-target inhibitors are promising for their reduced risk of drug resistance, higher efficacy, lower dosage, and fewer adverse events than those of single-target inhibitors. Hence, we present the synergistic mechanism underlying the role of EGFR dual-target inhibitors against drug resistance, their structure–activity relationships, and their therapeutic potential. Most importantly, we emphasize the optimal target combinations and design strategies for EGFR dual-target inhibitors and provide some perspectives on new challenges and future directions in this field.

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“…Hossam et al have published that the anilino-furo [2,3-d]pyrimidine derivatives they synthesized have EGFR tyrosine kinase inhibitory and anti-cancer effects [ 17 ]. Han et al stated that the chiral 6-aryl-furo [2,3-d]pyrimidine-4-amines they synthesized are equipotent to Erlonitib, which is an EGFR tyrosine kinase inhibitor and is used as an anticancer drug [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Novel N-benzyl-2-oxo-1,2-dihydrofuro [3,4-d]pyrimidine-3(4H)-carboxamide as anticancer agent: Synthesis, drug-likeness, ADMET profile, DFT and molecular modelling against EGFR target

Yılmaz

Uluçam

2023

Heliyon

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Discovery of anilino-furo[2,3- d ]pyrimidine derivatives as dual inhibitors of EGFR/HER2 tyrosine kinase and their anticancer activity

Cited by 32 publications

References 43 publications

A Review on Fused Pyrimidine Systems as EGFR Inhibitors and Their Structure–Activity Relationship

A Review on Fused Pyrimidine Systems as EGFR Inhibitors and Their Structure–Activity Relationship

Development of Dual Inhibitors Targeting Epidermal Growth Factor Receptor in Cancer Therapy

Novel N-benzyl-2-oxo-1,2-dihydrofuro [3,4-d]pyrimidine-3(4H)-carboxamide as anticancer agent: Synthesis, drug-likeness, ADMET profile, DFT and molecular modelling against EGFR target

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