Design, synthesis and structure-activity relationship of diaryl-ureas with novel isoxazol[3,4-b]pyridine-3-amino-structure as multi-target inhibitors against receptor tyrosine kinase

Shi, Zhi‐Hao; Liu, Feng-Tao; Tian, Hao-Zhong; Zhang, Yanmin; Li, Nian‐Guang; Lü, Tao

doi:10.1016/j.bmc.2018.08.013

Cited by 17 publications

(10 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RNA-ligand docking, molecular dynamics simulation showed that regorafenib can directly bind to miR-21 pre-element [93]. Docking studies of linifanib with FLT3 were recently reported, evidencing that 3-amino-indazole interacts with the ATP-bind site [61]. Kajal et al (2018) has reported the 2D co-crystal-binding conformation of VEGFR2-Tivozanib, in which tivozanib mimics the binding pattern of ATP [94].…”

Section: Mechanisms Of Inhibition Of Diarylureasmentioning

confidence: 99%

See 1 more Smart Citation

Diarylureas as Antitumor Agents

et al. 2021

View full text Add to dashboard Cite

The diarylurea is a scaffold of great importance in medicinal chemistry as it is present in numerous heterocyclic compounds with antithrombotic, antimalarial, antibacterial, and anti-inflammatory properties. Some diarylureas, serine-threonine kinase or tyrosine kinase inhibitors, were recently reported in literature. The first to come into the market as an anticancer agent was sorafenib, followed by some others. In this review, we survey progress over the past 10 years in the development of new diarylureas as anticancer agents.

show abstract

Section: Mechanisms Of Inhibition Of Diarylureasmentioning

confidence: 99%

“…Linifanib (ABT-869, Abbott Laboratories, Abbott Park, IL, USA, Figure 3) is an orally available TKI which targets VEGFR and PDGFR with relevant specificity and low off-target inhibition. Linifanib can also inhibit FLT-3 [61]. It does not show significant activity against representative cytosolic tyrosine and serine/threonine kinases [62].…”

Section: Linifanibmentioning

confidence: 99%

Diarylureas as Antitumor Agents

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Its inhibition has been found to stop transformation, proliferation, migration, differentiation, and metastasis of cancer cells. To improve the efficacy of Abbott’s Linifanib, 61 Shi et al reported a diaryl-urea with isoxazol[3,4-b]pyridine-3-amino-derivative 62 with inhibition potentials of 4 nM, 3 nM, and 8 nM against fms related receptor tyrosine kinase 3 (FLT3), kinase insert domain receptor (KDR), and platelet-derived growth factor receptor beta (PDGFR-β), respectively [ 69 , 70 ]. In another study, Jinfeng Wang and co-workers discovered two triple inhibition chemotypes, 63 and 64 ( Figure 6 ) from screening of these compounds derived from reaction between biphenyl-aryl urea and salicylaldoxime [ 71 ].…”

Section: Heterocyclic Compoundsmentioning

confidence: 99%

Synthetic and Naturally Occurring Heterocyclic Anticancer Compounds with Multiple Biological Targets

et al. 2021

View full text Add to dashboard Cite

Cancer is a complex group of diseases initiated by abnormal cell division with the potential of spreading to other parts of the body. The advancement in the discoveries of omics and bio- and cheminformatics has led to the identification of drugs inhibiting putative targets including vascular endothelial growth factor (VEGF) family receptors, fibroblast growth factors (FGF), platelet derived growth factors (PDGF), epidermal growth factor (EGF), thymidine phosphorylase (TP), and neuropeptide Y4 (NY4), amongst others. Drug resistance, systemic toxicity, and drug ineffectiveness for various cancer chemo-treatments are widespread. Due to this, efficient therapeutic agents targeting two or more of the putative targets in different cancer cells are proposed as cutting edge treatments. Heterocyclic compounds, both synthetic and natural products, have, however, contributed immensely to chemotherapeutics for treatments of various diseases, but little is known about such compounds and their multimodal anticancer properties. A compendium of heterocyclic synthetic and natural product multitarget anticancer compounds, their IC50, and biological targets of inhibition are therefore presented in this review.

show abstract

Section: Small-molecule Flt3 Inhibitorsmentioning

confidence: 99%

“…Enlightened by favorable clinical efficacy of multitarget TKIs for cancer treatment, our group designed and synthesized two series of diaryl-ureas with novel isoxazol[3,4-b] pyridine-3amino-structure through the bioisosterism strategy based on the lead compound Linifanib (ABT-869, Abbott), which was an oral active multitarget RTK inhibitor of KDR (VEGFR2), PDGFR-β, and CSF-1R. 100 Preliminary biological evaluations indicated that compound Li-S21 was a superb inhibitor against FLT3, KDR, and PDGFR-β (IC 50 = 4, 3, and 8 nM, respectively), as well as various cancer cell lines (Figure 10a). Molecular docking analysis demonstrated that the nitrogen atom and oxygen atom in the isoxazole ring formed two hydrogen bonds with Cys694, the amino group interacts with Glu692, and the urea part formed hydrogen bonds with Asp829 and Glu661, respectively (Figure 10b).…”

Section: Small-molecule Flt3 Inhibitorsmentioning

confidence: 99%

Small-Molecule Fms-like Tyrosine Kinase 3 Inhibitors: An Attractive and Efficient Method for the Treatment of Acute Myeloid Leukemia

et al. 2020

Self Cite

View full text Add to dashboard Cite

Fms-like tyrosine kinase 3 (FLT3) is an important member of the class III receptor tyrosine kinase (RTK) family, which is involved in the proliferation of hematopoietic cells and lymphocytes. In recent years, increasing evidence have demonstrated that the activation and mutation of FLT3 is closely implicated in the occurrence and development of acute myeloid leukemia (AML). The exploration of small-molecule inhibitors targeting FLT3 has aroused wide interest of pharmaceutical chemists and is expected to bring new hope for AML therapy. In this review, we specifically highlighted FLT3 mediated JAK/STAT, RAS/MAPK, and PI3K/AKT/mTOR signaling. The structural properties and biological activities of representative FLT3 inhibitors reported from 2014 to the present were also summarized. In addition, the major challenges in the current advance of novel FLT3 inhibitors were further analyzed, with the aim to guide future drug discovery.

show abstract

Design, synthesis and structure-activity relationship of diaryl-ureas with novel isoxazol[3,4-b]pyridine-3-amino-structure as multi-target inhibitors against receptor tyrosine kinase

Cited by 17 publications

References 29 publications

Diarylureas as Antitumor Agents

Diarylureas as Antitumor Agents

Synthetic and Naturally Occurring Heterocyclic Anticancer Compounds with Multiple Biological Targets

Small-Molecule Fms-like Tyrosine Kinase 3 Inhibitors: An Attractive and Efficient Method for the Treatment of Acute Myeloid Leukemia

Contact Info

Product

Resources

About