- INHIBITORS OF HISTONE DEACETYLASE USEFUL FOR THE TREATMENT OR PREVENTION OF HIV INFECTION
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The present invention relates to Compounds of Formula (I): Formula (I) and pharmaceutically acceptable salts or prodrug thereof, wherein R1, R2, R3, Ra, Rb, A and B are as defined herein. The present invention also relates to compositions comprising at least one compound of Formula (I), and methods of using the compounds of Formula (I) for treating or preventing HIV infection in a subject.
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Page/Page column 29; 30
(2020/02/23)
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- Selective Class i HDAC Inhibitors Based on Aryl Ketone Zinc Binding Induce HIV-1 Protein for Clearance
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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.
- 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
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supporting information
p. 1476 - 1483
(2020/07/31)
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- NOVEL TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS
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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.
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Paragraph 0380; 0381
(2016/07/27)
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- TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS
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The present invention is directed to tricyclic compounds (I), pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.
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Page/Page column 82
(2015/07/15)
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- Total synthesis of (+)-ileabethoxazole via an iron-mediated pauson-khand [2 + 2 + 1] carbocyclization
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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.
- Williams, David R.,Shah, Akshay A.
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supporting information
p. 8829 - 8836
(2014/07/07)
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- Substituted heterocyclylisoquinolinium salts and compositions and method of use thereof
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Substitutued heterocyclylisoquinolinium salts, pharmaceutical compositions containing them and methods for the treatment or prevention of neurodegenerative disorders or neurotoxic injuries utilizing them.
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- Substituted 6,11-ethano-6,11-dihydrobenzo[b] quinolizinium salts and compositions and methods of use thereof
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Substituted 6,11-ethano-6,11-dihydrobenzo[b]quinolizinium salts, pharmaceutical compositions containing them, and methods for the treatment of neurodegenerative disorders or neurotoxic injuries utilizing them, wherein the substituted 6,11-ethano-6,11-dihydrobenzo[b]quinolizinium salts have the formula: STR1 wherein: R1, R2, R3, R4, R5, R6, R7, X and p are as defined in the specification.
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