1,4-Dioxane-fused 4-anilinoquinazoline as inhibitors of epidermal growth factor receptor kinase

Lee, Jae Yeol; Park, Yong Kyu; Seo, Seon Hee; So, In-Seop; Chung, Heekyung; Yang, Beom-Seok; Lee, Sook Ja; Park, Hokoon; Lee, Yong Sup

doi:10.1002/1521-4184(200112)334:11<357::aid-ardp357>3.0.co;2-q

Cited by 22 publications

(10 citation statements)

References 3 publications

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“…The extracellular ligand-binding region of the EGFR or the intracellular tyrosine kinase region can be targeted by specific anticancer agents, which may interfere with the signaling pathways that modulate mitogenic and other cancer-promoting responses such as cell motility, cell adhesion, invasion, and angiogenesis [88]. 4-anilinoquinazoline derivatives are examples of antitumor agents for which the mode of action is to inhibit the tyrosine kinase activity of EFGR via competitive binding at the ATP site of the enzyme, resulting in cancer cell growth inhibition [89]. Wang et al (2015) reported a series of ruthenium(II) cymene complexes of 4-anilinoquinazoline derivatives that showed dual-targeting properties, including a significant inhibitory activity of EGFR and a high affinity with DNA via a minor groove binding mode of interaction in different types of cancers including breast cancer [90].…”

Section: Other Ruthenium Complexes For the Treatment Of Hormone Recepmentioning

confidence: 99%

Rationally Designed Ruthenium Complexes for Breast Cancer Therapy

Golbaghi

Castonguay

2020

Molecules

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Since the discovery of the anticancer potential of ruthenium-based complexes, several species were reported as promising candidates for the treatment of breast cancer, which accounts for the greatest number of new cases in women every year worldwide. Among these ruthenium complexes, species containing bioactive ligand(s) have attracted increasing attention due to their potential multitargeting properties, leading to anticancer drug candidates with a broader range of cellular targets/modes of action. This review of the literature aims at providing an overview of the rationally designed ruthenium-based complexes that have been reported to date for which ligands were carefully selected for the treatment of hormone receptor positive breast cancers (estrogen receptor (ER+) or progesterone receptor (PR+)). In addition, this brief survey highlights some of the most successful examples of ruthenium complexes reported for the treatment of triple negative breast cancer (TNBC), a highly aggressive type of cancer, regardless of if their ligands are known to have the ability to achieve a specific biological function.

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Section: Other Ruthenium Complexes For the Treatment Of Hormone Recepmentioning

confidence: 99%

Rationally Designed Ruthenium Complexes for Breast Cancer Therapy

Golbaghi

Castonguay

2020

Molecules

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“…The inhibition studies of human EGFR tyrosine kinase activities were done using C-terminal human EGFR tyrosine kinase domain as described previously [ 26 ]. PYK2104 was synthesized as reported and used as a reference compound [ 26 ]. The concentration of inhibitor that gives 50% inhibition was designated as IC 50 value.…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Novel Pyrimido[4,5-d]pyrimidine CDK2 Inhibitors as Anti-tumor Agents

El-Moghazy

Ibrahim²,

Abdelgawad³

et al. 2011

Sci. Pharm.

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A series of 2,5,7-trisubstituted pyrimido[4,5-d]pyrimidine cyclin-dependent kinase (CDK2) inhibitors is designed and synthesized. 6-Amino-2-thiouracil is reacted with an aldehyde and thiourea to prepare the pyrimido[4,5-d]-pyrimidines. Alkylation and amination of the latter ones give different amino derivatives. These compounds show potent and selective CDK inhibitory activities and inhibit in vitro cellular proliferation in cultured human tumor cells.

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“…Substituted and/or fused bicyclic pyrimidine-containing scaffolds are privileged structures in medicinal chemistry with diverse bioactivities and success stories reported including the development of anticancer, anti-inflammatory, antiviral and antibacterial pyrimidine-based chemical entities [5][6][7][8][9][10][11][12][13] . Starting from fused-pyrimidine scaffolds known in anticancer agents, such as lapatinib (1, Figure 1), TAK285 (2, Figure 1), compound 3 (Figure 1), our team has identified 5-amino-4-pyrimidinol hit compound 4 out of a small library.…”

Section: Introductionmentioning

confidence: 99%

Reprofiling of pyrimidine-based DAPK1/CSF1R dual inhibitors: identification of 2,5-diamino-4-pyrimidinol derivatives as novel potential anticancer lead compounds

Farag

Hassan

Ahn

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Hybridization of reported weakly active antiproliferative hit 5-amino-4-pyrimidinol derivative with 2-anilino-4-phenoxypyrimidines suggests a series of 2,5-diamino-4-pyrimidinol derivatives as potential antiproliferative agents. Few compounds belonging to the proposed series were reported as CSF1R/DAPK1 inhibitors as anti-tauopathies. However, the correlation between CSF1R/DAPK1 signalling pathways and cancer progression provides motives to reprofile them against cancer therapy. The compounds were synthesised, characterized, and evaluated against M-NFS-60 cells and a kinase panel which bolstered predictions of their antiproliferative activity and suggested the involvement of diverse molecular targets. Compound 6e, the most potent in the series, showed prominent broad-spectrum antiproliferative activity inhibiting the growth of hematological, NSCLC, colon, CNS, melanoma, ovarian, renal, prostate and breast cancers by 84.1, 52.79, 72.15, 66.34, 66.48, 51.55, 55.95, 61.85, and 60.87%, respectively. Additionally, it elicited an IC50 value of 1.97 µM against M-NFS-60 cells and good GIT absorption with Pe value of 19.0 ± 1.1 × 10−6 cm/s (PAMPA-GIT). Molecular docking study for 6e with CSF1R and DAPK1 was done to help to understand the binding mode with both kinases. Collectively, compound 6e could be a potential lead compound for further development of anticancer therapies.

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1,4-Dioxane-fused 4-anilinoquinazoline as inhibitors of epidermal growth factor receptor kinase

Cited by 22 publications

References 3 publications

Rationally Designed Ruthenium Complexes for Breast Cancer Therapy

Rationally Designed Ruthenium Complexes for Breast Cancer Therapy

Design, Synthesis and Biological Evaluation of Novel Pyrimido[4,5-d]pyrimidine CDK2 Inhibitors as Anti-tumor Agents

Reprofiling of pyrimidine-based DAPK1/CSF1R dual inhibitors: identification of 2,5-diamino-4-pyrimidinol derivatives as novel potential anticancer lead compounds

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