Synthesis and biological evaluation of heterocyclic bis-aryl amides as novel Src homology 2 domain containing protein tyrosine phosphatase-2 (SHP2) inhibitors
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Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
This work was supported by National Natural Science Foundation of China (21772068), National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program”, China (Number: 2018ZX09711002), the Natural Science Foundation of Jiangsu Province (BK20190608) and Jiangsu Province Postdoctoral Science Foundation (2019K220).
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2024, European Journal of Medicinal ChemistrySynthesis and biological evaluation of 2,5-diaryl-1,3,4-oxadiazole derivatives as novel Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) inhibitors
2021, Bioorganic ChemistryCitation Excerpt :Our efforts to develop modulators of protein tyrosine phosphatases (PTPs) started from 1H to 2,3-Dihydroperimidines [30–35]. Using the scaffold hopping strategy, we developed aromatic amides, heterocyclic bis-aryl amides [32] and benzo[c][1,2,5]thiadiazoles as SHP2 inhibitors [33]. To explore novel scaffolds for modulators of PTPs, in particular, the highly disease-relevant SHP2, we designed and synthesized a series of 2,5-diaryl-1,3,4-oxadiazole derivatives (Fig. 1), evaluated their inhibitory activities against SHP2.
Targeting SHP2 as a therapeutic strategy for inflammatory diseases
2021, European Journal of Medicinal ChemistryCitation Excerpt :Compared with SHP099 (IC50 = 19.86 μM), compound 3 (IC50 = 2.35 μM) showed a better inhibitory effect on BA/F3 cells under the same experimental conditions. Rajendran satheeshkumar et al. [147] designed and synthesized 11 heterocyclic diarylamide derivatives by replacing benzene ring with heterocycle in PTP1B inhibitor 1 [148]. Among them, compound 4 (Fig. 10) showed four-times higher inhibitory effect on SHP2 (IC50 = 2.63 ± 0.08 μM) than Na3VO4, and had no inhibitory activity on SHP1 and PTP1B.
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These authors contributed equally to this work.