946601-96-3Relevant academic research and scientific papers
Design, synthesis and biological evaluation of novel indazole-based derivatives as potent HDAC inhibitors via fragment-based virtual screening
Gao, Liang,Gao, Lina,He, Fengjun,Hu, Lihong,Kang, Di,Liu, Jian,Wang, Ping,Wen, Yu,Zhou, Jingxian
, (2020)
Based on fragment-based virtual screening and bioisoterism strategies, novel indazole and pyrazolo[3,4-b] pyridine derivatives as HDACs inhibitors were designed, synthesized and evaluated. Most of these compounds displayed good to excellent inhibitory activities against HDACs, especially compounds 15k and 15m were identified as potent inhibitors of HDAC1 (IC50 = 2.7 nM and IC50 = 3.1 nM), HDAC2 (IC50 = 4.2 nM and IC50 = 3.6 nM) and HDAC8 (IC50 = 3.6 nM and IC50 = 3.3 nM). Further anti-proliferation assays revealed that compounds 15k and 15m showed better anti-proliferative activities against HCT-116 and HeLa cells than positive control SAHA. The western blot analysis results indicated that compounds 15k and 15m noticeably up-regulated the level of acetylated α-tubulin and histone H3. In addition, the two compounds 15k and 15m could arrest cell cycle in G2/M phase and promote cell apoptosis, which was similar as the reference compound SAHA. Through the molecular docking and dynamic studies, the potent HDAC inhibitory activities mainly caused by van der Waals and electrostatic interactions with the HDACs.
Design, synthesis, and biological evaluation of indazole derivatives as selective and potent FGFR4 inhibitors for the treatment of FGF19-driven hepatocellular cancer
Chen, Xiaolu,Liu, Yanan,Zhang, Liting,Chen, Daoxing,Dong, Zhaojun,Zhao, Chengguang,Liu, Zhiguo,Xia, Qinqin,Wu, Jianzhang,Chen, Yongheng,Zheng, Xiaohui,Cai, Yuepiao
supporting information, (2021/02/26)
Fibroblast growth factor receptor 4 (FGFR4) is a member of the fibroblast growth factor receptor family, which is closely related to the occurrence and development of hepatocellular carcinoma (HCC). In this article, a series of indazole derivatives were designed and synthesized by using computer-aided drug design (CADD) and structure-based design strategies, and then they were evaluated for their inhibition of FGFR4 kinase and antitumor activity. F-30 was subtly selective for FGFR4 compared to FGFR1; it affected cell growth and migration by inhibiting FGFR4 pathways in HCC cell lines in a dose-dependent manner.
A facile method for the synthesis of nicotinonitriles from ketones via a one-pot chloromethyleneiminium salt mediated three-component reaction
Asokan,Anabha,Thomas, Ajith Dain,Jose, Ann Maria,Lethesh,Prasanth,Krishanraj
, p. 5641 - 5643 (2008/02/10)
Simple enolizable ketones such as acetophenones and benzalacetones were treated with malononitrile under Vilsmeier-Haack reaction conditions to afford 2-chloronicotinonitriles. The reaction proceeds via a one-pot chloromethyleneiminium salt mediated three
6-Aryl-pyrazolo[3,4-b]pyridines: Potent inhibitors of glycogen synthase kinase-3 (GSK-3)
Witherington, Jason,Bordas, Vincent,Gaiba, Alessandra,Garton, Neil S.,Naylor, Antoinette,Rawlings, Anthony D.,Slingsby, Brian P.,Smith, David G.,Takle, Andrew K.,Ward, Robert W.
, p. 3055 - 3057 (2007/10/03)
A novel series of 6-aryl-pyrazolo[3,4-b]pyridines has been identified that are potent inhibitors of glycogen synthase kinase-3 (GSK-3).
