170486-48-3Relevant articles and documents
Selective Class i HDAC Inhibitors Based on Aryl Ketone Zinc Binding Induce HIV-1 Protein for Clearance
Barnard, Richard J. O.,Carroll, Steve,Chung, Christine C.,Clausen, Dane,Duffy, Joseph L.,Fells, James,Holloway, M. Katharine,Howell, Bonnie J.,Kelly, Joseph,Kim, Hyunjin,Klein, Daniel J.,Kozlowski, Joseph A.,Liu, Jian,Myers, Robert W.,Wu, Guoxin,Wu, Jin,Yu, Wensheng,Yu, Younong
supporting information, p. 1476 - 1483 (2020/07/31)
HIV persistence in latently infected, resting CD4+ T cells is broadly considered a barrier to eradicate HIV. Activation of the provirus using latency-reversing agents (LRAs) followed by immune-mediated clearance to purge reservoirs has been touted as a promising therapeutic approach. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) control the acetylation level of lysine residues in histones to regulate the gene transcription. Several clinical HDAC inhibitors had been examined as LRAs, which induced HIV activation in vitro and in vivo. Here we report the discovery of a series of selective and potent class I HDAC inhibitors based on aryl ketones as a zinc binding group, which reversed HIV latency using a Jurkat model of HIV latency in 2C4 cells. The SAR led to the discovery of a highly selective class I HDAC inhibitor 10 with excellent potency. HDACi 10 induces the HIV gag P24 protein in patient latent CD4+ T cells.
NOVEL TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS
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Paragraph 0380; 0381, (2016/07/27)
The present invention is directed to tricyclic compounds, pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.
Total synthesis of (+)-ileabethoxazole via an iron-mediated pauson-khand [2 + 2 + 1] carbocyclization
Williams, David R.,Shah, Akshay A.
supporting information, p. 8829 - 8836 (2014/07/07)
Studies describe the total synthesis of (+)-ileabethoxazole (1) using a Stille cross-coupling reaction of propargylic stannanes with 5-iodo-1,3-oxazoles to produce 1,1-disubstituted allenes (11). An iron-mediated [2 + 2 + 1] carbocyclization yields a novel cyclopentenone for elaboration to 1. Site-selective palladium insertion reactions allow for regiocontrolled substitutions of the heterocycle. Asymmetric copper hydride reductions are examined, and strategies for the formation of the central aromatic ring are discussed.
