5057-52-3Relevant academic research and scientific papers
Identification of 5-Substituted 2-Acylaminothiazoles That Activate Tat-Mediated Transcription in HIV-1 Latency Models
Nguyen, William,Jacobson, Jonathan,Jarman, Kate E.,Jousset Sabroux, Helene,Harty, Leigh,McMahon, James,Lewin, Sharon R.,Purcell, Damian F.,Sleebs, Brad E.
, p. 5148 - 5175 (2019/05/28)
The persistent reservoir of cells latently infected with human immunodeficiency virus (HIV)-integrated proviral DNA necessitates lifelong suppressive antiretroviral therapy (ART). Epigenetic targeted compounds have shown promise as potential latency-reversing agents; however, these drugs have undesirable toxicity and lack specificity for HIV. We utilized a novel HEK293-derived FlpIn dual-reporter cell line, which quantifies specific HIV provirus reactivation (LTR promoter) relative to nonspecific host cell gene expression (CMV promoter), to identify the 5-substituted 2-acylaminothiazole hit class. Here, we describe the optimization of the hit class, defining the functionality necessary for HIV gene activation and for improving in vitro metabolism and solubility. The optimized compounds displayed enhanced HIV gene expression in HEK293 and Jurkat 10.6 latency cellular models and increased unspliced HIV RNA in resting CD4+ T cells isolated from HIV-infected individuals on ART, demonstrating the potential of the 2-acylaminothiazole class as latency-reversing agents.
COMPOUNDS AND COMPOSITIONS FOR DELIVERING ACTIVE AGENTS
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Page/Page column 23-24, (2008/06/13)
The present invention provides delivery agent compounds, compositions containing delivery agent compounds and an active agent and methods for delivering active agents, such as biologically or chemically active agents.
NOVEL THIOPHENE DERIVATIVES WHICH ARE HM74A AGONISTS
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Page/Page column 16, (2010/11/26)
The invention is concerned with novel substituted thiophene derivatives of formula (I) wherein R1 to R8, X, m and n are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds are HM74A agonists and can be used as medicaments.
Synthesis and structure-activity relationships of new ACAT inhibitors
Nioche, J. Y.,Decerprit, J.,Festal, D.
, p. 377 - 386 (2007/10/02)
A series of heterocyclic ureas were synthesized and their ability to inhibit arterial and intestinal ACAT was assessed in animals.The structural modifications carried out in this series led to N2-(2,4-difluorophenyl)-N1-8-(4-fluorophenyl)-2,3,4,5-tetrahydro-1-benzoxepin-5-yl-N1-n-heptylurea 21, which proved to be very active on both the inhibition of aortic ACAT and the inhibition of rat cholesterol intestinal absorption, thus exhibiting a strong hypocholesterolemic effect po in rat (ED25 = 0.2 mg/kg). aortic ACAT / intestinal inhibition / benzoxepin / urea / cholesterol / hypocholesterolaemic activity
