3-Hydroxyisoindolin-1-one derivates: Synthesis by palladium-catalyzed C H activation as BRD4 inhibitors against human acute myeloid leukemia (AML) cells
Bioorganic Chemistry, ISSN: 0045-2068, Vol: 86, Page: 119-125
2019
- 14Citations
- 8Captures
Metric Options: CountsSelecting the 1-year or 3-year option will change the metrics count to percentiles, illustrating how an article or review compares to other articles or reviews within the selected time period in the same journal. Selecting the 1-year option compares the metrics against other articles/reviews that were also published in the same calendar year. Selecting the 3-year option compares the metrics against other articles/reviews that were also published in the same calendar year plus the two years prior.
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations14
- Citation Indexes14
- 14
- CrossRef9
- Captures8
- Readers8
Article Description
Bromodomain protein 4 (BRD4) is a member of the bromodomain and extra-terminal domain (BET) protein family, which plays a key role in transcriptional regulation. Recent biological and pharmacological studies have enabled linking of the BET bromodomains with diseases, including inflammation and cancer, suggesting that bromodomains are druggable targets. In this study, we made further structural modifications of our previously reported BRD4 inhibitors, to develop new chemical scaffold 3-Hydroxyisoindolin-1-One. Then a series of compounds ( 10a-q ) were synthesized via palladium-catalyzed C H activation and BRD4-inhibitory activities and anti-proliferative effects of these compounds were evaluated. Compound 10e exhibited excellent BRD4-inhibitory activity with IC 50 value of 80 nM and anti-proliferation potency with IC 50 value of 365 nM in HL-60 (human promyelocytic leukemia) cancer cell lines. We have demonstrated compound 10e modulated the intrinsic apoptotic pathway. In conclusion, these results suggested that compound 10e could be utilized as a BRD4 inhibitor for further leukemia treatment.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S004520681830974X; http://dx.doi.org/10.1016/j.bioorg.2019.01.034; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85060453761&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/30690335; https://linkinghub.elsevier.com/retrieve/pii/S004520681830974X; https://dx.doi.org/10.1016/j.bioorg.2019.01.034
Elsevier BV
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