Design and synthesis of new lenalidomide analogs via Suzuki cross‐coupling reaction
| Autor: | Wei Lu, Jiyu Jin, Yubo Zhou, Han‐lin Wang, Donghuai Xiao, Wang Yujie, Jia Li |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Pharmaceutical Science
Antineoplastic Agents Tumor cells 01 natural sciences Coupling reaction Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Drug Discovery medicine Humans Methylene Lenalidomide IC50 Cell Proliferation Bioactive scaffold Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Cereblon Combinatorial chemistry In vitro 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry Drug Design Drug Screening Assays Antitumor medicine.drug |
| Zdroj: | Archiv der Pharmazie. 353:1900376 |
| ISSN: | 1521-4184 0365-6233 |
| DOI: | 10.1002/ardp.201900376 |
| Popis: | Lenalidomide is a cereblon modulator known for its antitumor, anti-inflammatory, and immunomodulatory properties in clinical applications. Recently, some reported lenalidomide analogs could exhibit a significant bioactivity through various modifications in the isoindolinone ring. In this study, we designed and synthesized a series of novel lenalidomide analogs on the basis of the installation of a methylene chain at the C-4 position of isoindolinone via the Suzuki cross-coupling reaction. These new compounds were further evaluated for their in vitro antiproliferative activities against two tumor cell lines (MM.1S and Mino). Specifically, compound 4c displayed the strongest antiproliferative activity against the MM.1S (IC50 = 0.27 +/- 0.03 mu M) and Mino (IC50 = 5.65 +/- 0.58 mu M) tumor cell lines. In summary, we have developed a new synthetic strategy for C-4 derivatization of lenalidomide, providing a bioactive scaffold that could be used to discover further potential antitumor lead compounds in pharmaceutical research. |
| Databáze: | OpenAIRE |
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