34687-03-1Relevant articles and documents
Substituted 1-methyl-4-phenylpyrrolidin-2-ones – Fragment-based design of N-methylpyrrolidone-derived bromodomain inhibitors
Hilton-Proctor, J. P.,Ilyichova, O.,Jennings, I. G.,Johnstone, R. W.,Mountford, S. J.,Scanlon, M. J.,Shortt, J.,Thompson, P. E.,Zheng, Z.
, (2020/03/03)
N-Methylpyrrolidone is one of several chemotypes that have been described as a mimetic of acetyl-lysine in the development of bromodomain inhibitors. In this paper, we describe the synthesis of a 4-phenyl substituted analogue – 1-methyl-4-phenylpyrrolidin-2-one – and the use of aryl substitution reactions as a divergent route for derivatives. Ultimately, this has led to structurally complex, chiral compounds with progressively improved affinity as inhibitors of bromodomain-containing protein 4.
Discovery of 3,4,6-Trisubstituted Piperidine Derivatives as Orally Active, Low hERG Blocking Akt Inhibitors via Conformational Restriction and Structure-Based Design
Dong, Xiaowu,Zhan, Wenhu,Zhao, Mengting,Che, Jinxin,Dai, Xiaoyang,Wu, Yizhe,Xu, Lei,Zhou, Yubo,Zhao, Yanmei,Tian, Tian,Cheng, Gang,Jin, Zegao,Li, Jia,Shao, Yanfei,He, Qiaojun,Yang, Bo,Weng, Qinjie,Hu, Yongzhou
supporting information, p. 7264 - 7288 (2019/08/20)
A series of 3,4-disubstituted piperidine derivatives were obtained based on a conformational restriction strategy and a lead compound, A12, that exhibited potent in vitro and in vivo antitumor efficacies; however, obvious safety issues limited its further development. Thus, systematic exploration of the structure-activity relationship of compound A12, involving the phenyl group, hinge-linkage, and piperidine moiety, led to the discovery of the superior 3,4,6-trisubstituted piperidine derivative E22. E22 showed increased potency in Akt1 and cancer cell inhibition, remarkably reduced human ether-a-go-go-related gene blockage, and significantly improved safety profiles. Compound E22 also exhibited good kinase selectivity, had a good pharmacokinetic profile, and displayed very potent in vivo antitumor efficacy, with over 90% tumor growth inhibition in the SKOV3 xenograft model. Further mechanistic studies were conducted to demonstrate that compound E22 could significantly inhibit the phosphorylation of proteins downstream of Akt kinase in cells and tumor tissue from the xenograft model.
A process for preparing 3 - phenyl - 4 - aminobutyric acid hydrochloride process (by machine translation)
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Paragraph 0035; 0036; 0037, (2018/01/02)
The present invention provides a process for preparing 3 - phenyl - 4 - aminobutyric acid hydrochloride of the process, the use of cinnamic acid methyl ester and nitromethane as the reaction substrate, nitromethane can be used as the reaction substrate bu