4068-76-2Relevant articles and documents
Design and synthesis of benzofuro[3,2-b]pyridin-2(1H)-one derivatives as anti-leukemia agents by inhibiting Btk and PI3Kδ
Liu, Linyi,Shi, Bingyu,Li, Xinyu,Wang, Xiangqian,Lu, Xiang,Cai, Xuerong,Huang, Ali,Luo, Guoshun,You, Qidong,Xiang, Hua
, p. 4537 - 4543 (2018)
Btk inhibitors and PI3Kδ inhibitors play crucial roles in the treatment of leukemia, and studies confirmed that the synergetic inhibition against Btk and PI3Kδ could gain an optimal response. Herein, a series of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives were designed and synthesized as dual Btk/PI3Kδ kinases inhibitors for the treatment of leukemia. Studies indicated that most compounds could suppress the proliferation of multiple leukemia or lymphoma cells (Raji, HL60 and K562 cells) at low micromolar concentrations in vitro. Further kinase assays identified several compounds could simultaneously inhibit Btk kinase and PI3Kδ kinase. Thereinto, compound 16b exhibited the best inhibitory activity (Btk: IC50 = 139 nM; PI3Kδ: IC50 = 275 nM) and showed some selectivity against PI3Kδ compared to PI3Kβ/γ. Finally, the SAR of target compounds was preliminarily discussed combined with docking results. In brief, 16b possessed of the potency for the further optimization as anti-leukemia drugs by inhibiting simultaneously Btk kinase and PI3Kδ kinase.
Multigram Synthesis of Tetrasubsituted Dihydrobenzofuran GSK973 Enabled by High-Throughput Experimentation and a Claisen Rearrangement in Flow
Alder, Catherine M.,Gray, Matthew,Huff, Chelsea A.,Manning, Calvin O.,Preston, Alex,Rushworth, Philip,Shuster, Leanna E.,Watson, Robert J.,Wheelhouse, Katherine M. P.,Williams, Glynn D.,Demont, Emmanuel H.
, p. 365 - 379 (2022/02/10)
This article describes two routes toward the synthesis of cis or trans C2,3,5,7-tetrasubstituted dihydrobenzofurans as potent and selective bromodomain and extra-terminal BD2 inhibitors, followed by the optimization of the synthesis of the lead molecule GSK973 to support pre-clinical efficacy and safety studies. The use of flow chemistry for a Claisen rearrangement, extensive optimization of the fluorination step, and high-yielding aminocarbonylation were key to generate the required 50 g of material. The identified new route also represents a robust starting point for further optimization.
SMALL MOLECULES TARGETING MUTANT MAMMALIAN PROTEINS
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Paragraph 0593; 0594, (2021/12/03)
Disclosed are compounds, compositions, and methods useful for treating or preventing a disease or disorder associated with a mutation in a protein.
Synthesis, structure and in vitro cytotoxicity testing of some 2-aroylbenzofuran-3-ols
Anh, Dang Thi Tuyet,Cong, Nguyen Tien,Dat, Nguyen Dang,Dung, Pham Duc,Meervelt, Luc Van,Phuong, Tran Hoang,Trang, Huynh Thi Xuan,Trung, Vu Quoc,Tuyen, Nguyen Van
, p. 874 - 882 (2020/09/23)
Five 2-aroyl-5-bromobenzo[b]furan-3-ol compounds (two of which are new) and four new 2-aroyl-5-iodobenzo[b]furan-3-ol compounds were synthesized starting from salicylic acid. The compounds were characterized by mass spectrometry and 1H NMR and 13C NMR spectroscopy. Single-crystal X-ray diffraction studies of four compounds, namely, (5-bromo-3-hydroxybenzofuran-2-yl)(4-fluorophenyl)methanone, C15H8BrFO3, (5-bromo-3-hydroxybenzofuran-2-yl)(4-chlorophenyl)methanone, C15H8BrClO3, (5-bromo-3-hydroxybenzofuran-2-yl)(4-bromophenyl)methanone, C15H8Br2O3, and (4-bromophenyl)(3-hydroxy-5-iodobenzofuran-2-yl)methanone, C15H8BrIO3, were also carried out. The compounds were tested for their in vitro cytotoxicity on the four human cancer cell lines KB, Hep-G2, Lu-1 and MCF7. Six compounds show good inhibiting abilities on Hep-G2 cells, with IC50 values of 1.39-8.03?μM.
