97382-57-5Relevant academic research and scientific papers
QUINOLINE DERIVATIVES AND USES IN MANAGING CANCER
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Page/Page column 117, (2021/03/19)
Provided herein are compounds, pharmaceutical compositions including such compounds, and methods of using such compounds to treat diseases or disorders associated with MDM2 activity.
Discovery of N-(3,4-Dimethylphenyl)-4-(4-isobutyrylphenyl)-2,3,3a,4,5,9b-hexahydrofuro[3,2- c]quinoline-8-sulfonamide as a Potent Dual MDM2/XIAP Inhibitor
Wu, Zhongzhi,Gu, Lubing,Zhang, Sicheng,Liu, Tao,Lukka, Pradeep B.,Meibohm, Bernd,Bollinger, John C.,Zhou, Muxiang,Li, Wei
, p. 1930 - 1950 (2021/03/01)
Murine double minute 2 (MDM2) and X-linked inhibitor of apoptosis protein (XIAP) are important cell survival proteins in tumor cells. As a dual MDM2/XIAP inhibitor reported previously, compound MX69 has low potency with an IC50 value of 7.5 μM against an acute lymphoblastic leukemia cell line EU-1. Herein, we report the structural optimization based on the MX69 scaffold, leading to the discovery of a 25-fold more potent analogue 14 (IC50 = 0.3 μM against EU-1). We demonstrate that 14 maintains its mode of action by dual targeting of MDM2 and XIAP through inducing MDM2 protein degradation and inhibiting XIAP mRNA translation, respectively, which resulted in cancer cell growth inhibition and cell death. The results strongly suggest that the scaffold based on 14 is promising for further optimization to develop a new therapeutic agent for leukemia and possibly other cancers where MDM2 and XIAP are dysregulated.
Pentamethylcyclopentadienide in organic synthesis: Nucleophilic addition of lithium pentamethylcyclopentadienide to carbonyl compounds and carbon-carbon bond cleavage of the adducts yielding the parent carbonyl compounds
Uemura, Minoru,Yagi, Kazunari,Iwasaki, Masayuki,Nomura, Kenichi,Yorimitsu, Hideki,Oshima, Koichiro
, p. 3523 - 3535 (2007/10/03)
Lithium pentamethylcyclopentadienide (C5Me5Li, Cp*Li) reacted with aromatic aldehyde to provide the corresponding carbinol in excellent yield. The carbinol returns to the parent aldehyde and pentamethylcyclopentadiene upon exposure to acid or due to heating. Chlorodimethylaluminum is essential as an additive to attain the nucleophilic addition of Cp*Li to aliphatic aldehyde. The carbinol derived from aliphatic aldehyde returns to the parent aldehyde and pentamethylcyclopentadiene by the action of a catalytic amount of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ). The reversible addition/elimination of the Cp* group can represent a protection of aldehyde. Mechanistic details of the carbon-carbon bond cleavage are also disclosed.
