Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors

Ye, Lianbao; Zhao, Tao; Du, Wenjun; Li, Anhu; Gao, Wei; Li, Jingrong; Wang, Ling; Chen, Weiqiang

doi:10.1080/14756366.2019.1634704

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…The compounds were provided by Guangdong Pharmaceutical University, which were prepared according to the references. [22][23][24][25][26][27]…”

Section: Methodsmentioning

confidence: 99%

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Anti‐Herpes Simplex Virus Type 1 Activity Evaluation of Natural Derived Phloroglucinol Derivatives and Their Molecular Mechanisms Study

Mai,

Li,

Luo

et al. 2023

Chemistry & Biodiversity

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HSV‐1 is a common infection that can cause cold sores. In this study, the anti‐HSV‐1 virus activity of three series compounds A1–A9, B1–B12, C1–C22 was screened by MTT assay, qRT‐PCR assay, Western blot assay and viruses’ plaque assays. The results of MTT assay disclosed that phloroglucinol derivatives C2 and C3 effectively inhibited the death of HSV‐1 infected vero cells with the CC50 values of C2 and C3 were 72.64 μmol/L and 32.62 μmol/L in HaCaT cells, 137.6 μmol/L and 48.55 μmol/L in Hela cells. The IC50 values of C3 in vero cells and Hela cells were 19.26 μmol/L and 22.98 μmol/L, respectively. In the qRT‐PCR experiments, it showed that C2 and C3 effectively reduced the synthesis of HSV‐1 early viral gene VP16 and late viral gene gD. The Western blot results showed that both C2 and C3 inhibited the expression of HSV‐1 gD protein in a concentration‐dependent manner. Lastly, viruses’ plaque assay results showed that C2 and C3 inhibited the production of HSV‐1 progeny virus in Hela cells and HaCaT cells in a concentration‐dependent manner. Taken together, these results suggest that C2 and C3 are promising candidate that warrants further attention in the development of anti‐HSV‐1 drugs.

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“…The compounds were provided by Guangdong Pharmaceutical University, which were prepared according to the references. [22][23][24][25][26][27]…”

Section: Methodsmentioning

confidence: 99%

“…The solvents and reagents were purchased from commercial vendors. The compounds were provided by Guangdong Pharmaceutical University, which were prepared according to the references [22–27] …”

Section: Methodsmentioning

confidence: 99%

Anti‐Herpes Simplex Virus Type 1 Activity Evaluation of Natural Derived Phloroglucinol Derivatives and Their Molecular Mechanisms Study

Mai,

Li,

Luo

et al. 2023

Chemistry & Biodiversity

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“…A series of 2,4-diamino-pyrimidine containing spiro structures were prepared and evaluated as dual EGFR and HER2 inhibitors under 0.5 M drug concentration. Compounds 8a,b showed the highest inhibitory effects against a panel of EGFR kinases especially against both mutants T790M and L858R EGFR kinases which were 31 times more stronger than neratinib as standard drug (IC 50 ranging from 0.05 to 0.2 μM) (Ye, et al 2019).…”

Section: 4-diamino-substituted Pyrimidine Derivativesmentioning

confidence: 96%

Recent Advances on Pyrimidine Derivatives as Anticancer Agents.

Mahdy,

Elnagar,

Sakr

2023

Al-Azhar Journal of Pharmaceutical Sciences

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Cancer is a global health challenge; it impacts the quality of life and its treatment is associated with several side effects. Resistance of the cancer cells to the existing drugs has led to search for novel anticancer agents. Pyrimidine, a privileged scaffold, is part of living organisms and plays vital role in various biological procedures as well as in cancer pathogenesis. Due to resemblance in structure with the nucleotide base pair of DNA and RNA, it is recognized as valuable compound in the treatment of cancer. ObjectivesMany novel pyrimidine derivatives have been designed and developed for their anticancer activity in the last few years. The present review aims to focus on the structure of pyrimidine derivatives as anticancer agent from the last decade. ResultsIn summary, the development of more potent and efficacious anticancer drugs with pyrimidine scaffold will continue to be a promising scaffold over the next 20 years.

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“…A series of 2,4-diamino-pyrimidine containing spiro structures were prepared and evaluated as dual EGFR and HER2 inhibitors under 0.5 M drug concentration. Compounds 15a,b showed the highest inhibitory effects against a panel of EGFR kinases especially against both mutants T790M and L858R EGFR kinases which were 31 times more stronger than neratinib as standard drug (IC50 ranging from 0.05 to 0.2 μM) (Ye, Zhao et al 2019).…”

Section: B-aminopyrimidine-based Derivativesmentioning

confidence: 97%

Recent Advances in Drugs Targeting Protein Kinases for Cancer Therapy.

Mahdy

Shaat

Ayyad

2022

Al-Azhar Journal of Pharmaceutical Sciences

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Cancer has continued to be utmost challenging and life-threatening diseases to treat. Worldwide, cancer has been proven to be a major cause of death after cardiovascular diseases. The development of new drugs that can be able to inhibit the proliferation of cancerous cells only with minimum or without any side effects on healthy cells is a quite challenging task. Protein kinases are enzymes located in the cytoplasm that phosphorylate proteins. Protein kinases mediate most of the signal transduction in eukaryotic cells and also control many other cellular processes, including metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, development, the immune response, nervous system function, apoptosis, and differentiation. Normally, the activity protein kinases are stringently regulated. However, under pathological conditions, deregulation of protein kinases can lead to altered kinase expression and functions, and the initiation and survival of tumors. Therefore, protein kinases are a very attractive target class for therapeutic interventions in many disease states such as cancer. Kinase inhibitors now account for a quarter of all current drug discovery research and development efforts. Therefore, researchers around the globe are involved in the development of more efficient and safer targeted kinase inhibitors. ObjectivesTo complement the published literature on clinical kinase inhibitors, we have prepared a review that recaps this large data set into an accessible format for the medicinal chemistry community. Here, we review the remarkable progress made over the past 20 years in improving the potency and specificity of small-molecule inhibitors of protein for cancer therapy. ResultsIn summary, the potential for developing novel types of kinase inhibitor is huge, and we confidently predict that this will continue to be a major growth area over the next 20 years,

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Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors

Cited by 7 publications

References 21 publications

Anti‐Herpes Simplex Virus Type 1 Activity Evaluation of Natural Derived Phloroglucinol Derivatives and Their Molecular Mechanisms Study

Anti‐Herpes Simplex Virus Type 1 Activity Evaluation of Natural Derived Phloroglucinol Derivatives and Their Molecular Mechanisms Study

Recent Advances on Pyrimidine Derivatives as Anticancer Agents.

Recent Advances in Drugs Targeting Protein Kinases for Cancer Therapy.

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