1859-41-2Relevant articles and documents
Design and synthesis of HDAC inhibitors to enhance the therapeutic effect of diffuse large B-cell lymphoma by improving metabolic stability and pharmacokinetic characteristics
Cui, Hao,Hong, Qianqian,Wei, Ran,Li, Hongmei,Wan, Chunyang,Chen, Xin,Zhao, Shuang,Bu, Haizhi,Zhang, Bingxu,Yang, Dexiao,Lu, Tao,Chen, Yadong,Zhu, Yong
, (2021/12/27)
Histone deacetylases (HDAC) are clinically validated and attractive epigenetic drug targets for human cancers. Several HDAC inhibitors have been approved for cancer treatment to date, however, clinical applications have been limited due to the poor pharmacokinetics, bioavailability, selectivity of the HDAC inhibitors and most of them need to be combined with other drugs to achieve better results. Here, we describe our efforts toward the discovery of a novel series of lactam-based derivatives as selective HDAC inhibitors. Intensive structural modifications lead to the identification of compound 24g as the most active Class I HDAC Inhibitor, along with satisfactory metabolic stability in vitro (t1/2, human = 797 min) and the desirable oral bioavailability (F = 92%). More importantly, compound 24g showed good antitumor efficacy in a TMD-8 xenograft model (TGI = 77%) without obvious toxicity. These results indicated that Class I HDAC Inhibitor could be potentially used to treat certain diffuse large B-cell lymphoma therapeutics.
SpinPhox/iridium(I)-catalyzed asymmetric hydrogenation of cyclic α-alkylidene carbonyl compounds
Liu, Xu,Han, Zhaobin,Wang, Zheng,Ding, Kuiling
supporting information, p. 1978 - 1982 (2014/03/21)
Optically active medium-sized cyclic carbonyl compounds bearing an α-chiral carbon center are of interest in pharmaceutical sciences and asymmetric synthesis. Herein, SpinPhox/IrI catalysts have been demonstrated to be highly enantioselective in the asymmetric hydrogenation of the Ci￡C bonds in the exocyclic α,β-unsaturated cyclic carbonyls, including a broad range of α-alkylidene lactams, unsaturated cyclic ketones, and lactones. It is noteworthy that the procedure can be successfully used in the asymmetric hydrogenation of the challenging α-alkylidenelactam substrates with six- or seven-membered rings, thus affording the corresponding optically active carbonyl compounds with an α-chiral carbon center in generally excellent enantiomeric excesses (up to 98 % ee). Synthetic utility of the protocol has also been demonstrated in the asymmetric synthesis of the anti-inflammatory drug loxoprofen and its analogue, as well as biologically important ε-aminocaproic acid derivatives. Take it for a spin: SpinPhox/IrI complexes are highly efficient and versatile in the enantioselective hydrogenation of a broad spectrum of exocyclic α,β-unsaturated carbonyl compounds, especially the challenging α-alkylidene lactam substrates with six- or seven-membered rings. The synthetic utility of the present protocol is demonstrated in the asymmetric synthesis of biologically important loxoprofen and ε-aminocaproic acid derivatives. Copyright
Wittig-Horner synthesis of N-acyl-?±-ylidene-?3-aminobutyrates and of 3- ylidene-2-pyrrolidones
Stamm,Baumann
, p. 885 - 888 (2007/10/03)
Wittig-Homer reaction of benzaldehyde and of ketones with recently described diethyl ?3-amido-?±-ethoxycarbonyl-phosphonates provides the title esters and/or the title pyrrolidones, namely both E- and Z-isomers from unsymmetrical carbonyl components. Ylidenpyrrolidones are directly and without by-products obtained from the recently described diethyl 1- ethoxycarbonyl-2-pyrrolidone-3-phosphonate.
