17449-76-2Relevant articles and documents
Trans-Selective and Switchable Arene Hydrogenation of Phenol Derivatives
Bergander, Klaus,Glorius, Frank,Heusler, Arne,Wollenburg, Marco
, p. 11365 - 11370 (2020/11/24)
A trans-selective arene hydrogenation of abundant phenol derivatives catalyzed by a commercially available heterogeneous palladium catalyst is reported. The described method tolerates a variety of functional groups and provides access to a broad scope of trans-configurated cyclohexanols as potential building blocks for life sciences and beyond in a one-step procedure. The transformation is strategically important because arene hydrogenation preferentially delivers the opposite cis-isomers. The diastereoselectivity of the phenol hydrogenation can be switched to the cis-isomers by employing rhodium-based catalysts. Moreover, a protocol for the chemoselective hydrogenation of phenols to cyclohexanones was developed.
Discovery of a Novel Piperidine-Based Inhibitor of Cholesteryl Ester Transfer Protein (CETP) That Retains Activity in Hypertriglyceridemic Plasma
Yamada, Ken,Brousseau, Margaret,Honma, Wataru,Iimura, Akiko,Imase, Hidetomo,Iwaki, Yuki,Kawanami, Toshio,Lasala, Daniel,Liang, Guiqing,Mitani, Hironobu,Nonomura, Kazuhiko,Ohmori, Osamu,Pan, Meihui,Rigel, Dean F.,Umemura, Ichiro,Yasoshima, Kayo,Zhu, Guoming,Mogi, Muneto
, p. 8466 - 8481 (2017/11/03)
Herein we describe the discovery and characterization of a novel, piperidine-based inhibitor of cholesteryl ester transfer protein (CETP) with a core structure distinct from other reported CETP inhibitors. A versatile synthesis starting from 4-methoxypyridine enabled an efficient exploration of the SAR, giving a lead molecule with potent CETP inhibition in human plasma. The subsequent optimization focused on improvement of pharmacokinetics and mitigation of off-target liabilities, such as CYP inhibition, whose improvement correlated with increased lipophilic efficiency. The effort led to the identification of an achiral, carboxylic acid-bearing compound 16 (TAP311) with excellent pharmacokinetics in rats and robust efficacy in hamsters. Compared to anacetrapib, the compound showed substantially reduced lipophilicity, had only modest distribution into adipose tissue, and retained potency in hypertriglyceridemic plasma in vitro and in vivo. Furthermore, in contrast to torcetrapib, the compound did not increase aldosterone secretion in human adrenocortical carcinoma cells nor in chronically cannulated rats. On the basis of its preclinical efficacy and safety profile, the compound was advanced into clinical trials.
A nitric oxide-dexamethasone and preparation method and use thereof
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Paragraph 0045; 0046, (2017/01/17)
The invention relates to nitric oxide donor type hexadecadrol as well as a preparation method and application thereof. The nitric oxide donor type hexadecadrol as a compound is obtained by enabling nitrous acid ester to be connected with hexadecadrol through ethyl cyclohexanecarboxylate; the in-vitro antiinflammatory activity of the nitric oxide donor type hexadecadrol is better than that of the hexadecadrol; besides, the nitric oxide donor type hexadecadrol can restrain the growth of methicillin-resistant staphylococcus aureus (MRSA) in vitro, restrain the formation of MRSA biomembrane, and lead to the death of bacteria in the MRSA biomembrane. In addition, the compound can notably increase the survival rate of mice in MRSA sepsis lethal models, reduces the inflammation pathology damage of the mice in sub-sepsis models, decreases the constant value number of bacteria, and has notable advantages in the respect of preventing and treating MRSA sepsis.
