157555-74-3Relevant academic research and scientific papers
Discovery of Potent and Selective CDK9 Degraders for Targeting Transcription Regulation in Triple-Negative Breast Cancer
Wei, Dan,Wang, Hanlin,Zeng, Qinghe,Wang, Wenjing,Hao, Bingbing,Feng, Xule,Wang, Peipei,Song, Ning,Kan, Weijuan,Huang, Guifang,Zhou, Xiaoyu,Tan, Minjia,Zhou, Yubo,Huang, Ruimin,Li, Jia,Chen, Xiao-Hua
supporting information, p. 14822 - 14847 (2021/10/12)
Triple-negative breast cancer (TNBC) is highly aggressive with very limited treatment options due to the lack of efficient targeted therapies and thus still remains clinically challenging. Targeting transcription-associated cyclin-dependent kinases to remodel transcriptional regulation shows great promise in cancer therapy. Herein, we report the synthesis, optimization, and evaluation of new series of heterobifunctional molecules as highly selective and efficacious CDK9 degraders, enabling potent inhibition of TNBC cell growth and rapidly targeted degradation of CDK9. Moreover, the most potent CDK9 degrader (compound 45) induces cell apoptosis in vitro and inhibits tumor growth in the MDA-MB-231 TNBC model. Furthermore, the RNA-seq, immunohistochemistry assays demonstrate that the CDK9 degrader downregulates the downstream targets, such as MYC, at the transcriptional level, resulting apoptosis in TNBC cells. Our work establishes that 45 is a highly potent and efficacious CDK9 degrader for targeting transcription regulation, which represents an effective strategy and great potential as a new targeted therapy for TNBC.
Titanium-mediated amination of Grignard reagents using primary and secondary amines
Barker, Timothy J.,Jarvo, Elizabeth R.
supporting information; experimental part, p. 8325 - 8328 (2011/10/31)
Make it, then break it: N-chlorosuccinimide (NCS) was employed as the oxidant in the synthesis of aniline derivatives using the title transformation (see scheme). Functionalization was well tolerated on both the amine and Grignard reagent. An androgen receptor agonist and several analogues were synthesized to demonstrate the utility of this method.
SUBSTITUTED AMINO ALCOHOLS
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Page/Page column 27, (2009/04/24)
Disclosed herein are substituted amino alcohol anti-mycobacterial agents and/or chelation therapy agents of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
Enantioselective synthesis of (S,S)-ethambutol using proline-catalyzed asymmetric α-aminooxylation and α-amination
Kotkar, Shriram P.,Sudalai, Arumugam
, p. 1738 - 1742 (2007/10/03)
An efficient enantioselective synthesis of (S,S)-ethambutol, a tuberculostatic antibiotic, has been achieved in 99% ee via both proline-catalyzed α-aminooxylation and α-amination of n-butyraldehyde as the key step.
