Design, synthesis and biological evaluation of 7-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)-2,3-dihydro-1H-inden-1-one derivatives as potent FAK inhibitors for the treatment of ovarian cancer

Wei, Wei; Feng, Zongyun; Liu, Zhihao; Li, Xinyue; He, Hualong; Ran, Kai; Shi, Yaojie; Zhu, Yiping; Ye, Tinghong; Gao, Chao; Wang, Ningyu; Yu, Luoting

doi:10.1016/j.ejmech.2021.113978

Cited by 15 publications

(6 citation statements)

References 39 publications

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“…Derivative 21 reduced PA-1 cell migration and invasion, decreased MMP-2 and MMP-9 expression and, when orally administered to mice, suppressed ovarian cancer growth and metastasis formation, without adverse effects. All these biological results underlined the potential of this compound for ovarian cancer treatment [ 53 ].…”

Section: Fak Inhibitorsmentioning

confidence: 98%

The Development of FAK Inhibitors: A Five-Year Update

Spallarossa

Tasso

Russo

et al. 2022

IJMS

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Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase over-expressed in different solid cancers. In recent years, FAK has been recognized as a new target for the development of antitumor agents, useful to contrast tumor development and metastasis formation. To date, studies on the role of FAK and FAK inhibitors are of great interest for both pharmaceutical companies and academia. This review is focused on compounds able to block FAK with different potencies and with different mechanisms of action, that have appeared in the literature since 2017. Furthermore, new emerging PROTAC molecules have appeared in the literature. This summary could improve knowledge of new FAK inhibitors and provide information for future investigations, in particular, from a medicinal chemistry point of view.

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Section: Fak Inhibitorsmentioning

confidence: 98%

The Development of FAK Inhibitors: A Five-Year Update

Spallarossa

Tasso

Russo

et al. 2022

IJMS

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“…Thirty-one pyrimidine derivatives synthesized by Wei et al were utilized to develop QSAR models. 26 The activity values (IC 50 in nM) were translated into the corresponding pIC 50 values (Àlog IC 50 ). With the help of SYBYL-X.2.0, all 31 molecules were sketched before being optimized utilizing the typical Tripos force field and the corresponding Gasteiger-Huckel atomic partial charges.…”

Section: Molecular Construction and Structure Optimizationmentioning

confidence: 99%

“…25 In the current study, 31 pyrimidine derivatives synthesized by Wei et al as FAK inhibitors, as shown in Scheme 1, were employed in an integrated computational methodology combining molecular docking, MD simulations, and 3D-QSAR methodologies. The ideal 3D-QSAR CoMSIA models were created and the most important structural characteristics 26 influencing the inhibitory actions were also discovered. Four new FAK inhibitors that exhibited greater activity were developed and evaluated for their pharmacokinetic characteristics (ADMET) and drug-likeness.…”

Section: Introductionmentioning

confidence: 99%

Computational investigation of novel pyrimidine derivatives as potent FAK inhibitorsvia3D-QSAR, molecular docking, molecular dynamics simulation and retrosynthesis

El Bahi,

Boutalaka,

El Alaouy

et al. 2023

New J. Chem.

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“…Wei et al [ 88 ] used scaffold-hopping strategies to design a series of pyrrolo[2,3-d]pyrimidine hybrids and evaluated their focal adhesion kinase (FAK) activity. Compound 93 (FAK, IC 50 = 1.9 nM) showed the best FAK activity of all the evaluated compounds.…”

Section: Six-membered Heterocyclic Compoundsmentioning

confidence: 99%

“…Also, the migration and tube formation of HUVECs in the anti-angiogenesis studies prevented the angiogenesis of zebrafish embryos in vivo (see Figure 20). Wei et al [88] used scaffold-hopping strategies to design a series of pyrrolo [2,3d]pyrimidine hybrids and evaluated their focal adhesion kinase (FAK) activity. Compound 93 (FAK, IC 50 = 1.9 nM) showed the best FAK activity of all the evaluated compounds.…”

Section: Pyrimidinementioning

confidence: 99%

An Overview of the Biological Evaluation of Selected Nitrogen-Containing Heterocycle Medicinal Chemistry Compounds

Ebenezer

Jordaan

Carena

et al. 2022

IJMS

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Heterocyclic compounds are a class of compounds of natural origin with favorable properties and hence have major pharmaceutical significance. They have an exceptional adroitness favoring their use as diverse smart biomimetics, in addition to possessing an active pharmacophore in a complex structure. This has made them an indispensable motif in the drug discovery field. Heterocyclic compounds are usually classified according to the ring size, type, and the number of heteroatoms present in the ring. Among different heterocyclic ring systems, nitrogen heterocyclic compounds are more abundant in nature. They also have considerable pharmacological significance. This review highlights recent pioneering studies in the biological assessment of nitrogen-containing compounds, namely: triazoles, tetrazoles, imidazole/benzimidazoles, pyrimidines, and quinolines. It explores publications between April 2020 and February 2022 and will benefit researchers in medicinal chemistry and pharmacology. The present work is organized based on the size of the heterocyclic ring.

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Design, synthesis and biological evaluation of 7-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)-2,3-dihydro-1H-inden-1-one derivatives as potent FAK inhibitors for the treatment of ovarian cancer

Cited by 15 publications

References 39 publications

The Development of FAK Inhibitors: A Five-Year Update

The Development of FAK Inhibitors: A Five-Year Update

Computational investigation of novel pyrimidine derivatives as potent FAK inhibitorsvia3D-QSAR, molecular docking, molecular dynamics simulation and retrosynthesis

An Overview of the Biological Evaluation of Selected Nitrogen-Containing Heterocycle Medicinal Chemistry Compounds

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