Spiro[azetidine-indolines] are important scaffolds in diverse bioactive compounds. Current efforts to synthesize spiro[azetidine-indolines] are limited to chiral spiro[azetidine-2,3'-indolines]. Asymmetric synthesis of structurally similar chiral spiro[azetidine-3,3'-indolines] remains unexplored. In this work, the first copper(I)catalyzed asymmetric Kinugasa/aryl CÀ C coupling cascade reaction is described. This provides a straightforward access to densely functionalized chiral spiro[azetidine-3,3'-indoline]-2,2'-diones in good yields and with high enantioselectivity.
An efficient and convenient synthesis of functionalized [1,2,4]triazolo[1,5-a]pyridines derivates is presented. The protocol is through a palladium catalyzed tandem C-N coupling/Boulton-Katritzky rearrangement process from 3-aminoisoxazoles or 1,2,4-oxadiazol-3-amines with 2-pyridyl trifluoromethanesulfonate....
A highly efficient and mild sequential nucleophilic addition/ cyclization/copper catalyzed CÀ N coupling reaction of o-iodophenyl isothiocyanates with propargylamines has been realized, which delivers a variety of benzimidazo [2,1-b]thiazole derivatives in good yields. Moreover, this protocol could be performed at gram scale and applied to the concise synthesis of tilomisole.
RIOK2
is an atypical kinase implicated in multiple human cancers.
Although recent studies establish the role of RIOK2 in ribosome maturation
and cell cycle progression, its biological functions remain poorly
elucidated, hindering the potential to explore RIOK2 as a therapeutic
target. Here, we report the discovery of CQ211, the most
potent and selective RIOK2 inhibitor reported so far. CQ211 displays a high binding affinity (K
d = 6.1 nM) and shows excellent selectivity to RIOK2 in both enzymatic
and cellular studies. It also exhibits potent proliferation inhibition
activity against multiple cancer cell lines and demonstrates promising
in vivo efficacy in mouse xenograft models. The crystal structure
of RIOK2-CQ211 sheds light on the molecular mechanism
of inhibition and informs the subsequent optimization. The study provides
a cell-active chemical probe for verifying RIOK2 functions, which
may also serve as a leading molecule in the development of therapeutic
RIOK2 inhibitors.
Spiro[azetidine-indolines] are important scaffolds in diverse bioactive compounds. Current efforts to synthesize spiro[azetidine-indolines] are limited to chiral spiro[azetidine-2,3'-indolines]. Asymmetric synthesis of structurally similar chiral spiro[azetidine-3,3'-indolines] remains unexplored. In this work, the first copper(I)catalyzed asymmetric Kinugasa/aryl CÀ C coupling cascade reaction is described. This provides a straightforward access to densely functionalized chiral spiro[azetidine-3,3'-indoline]-2,2'-diones in good yields and with high enantioselectivity.
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