30297-87-1Relevant academic research and scientific papers
Diversity-orientated synthesis of macrocyclic heterocycles using a double SNAr approach
Carbajo, Rodrigo J.,McCoull, William,Raubo, Joanna,Raubo, Piotr,Thomas, Morgan
, p. 6274 - 6290 (2021/07/28)
An efficient macrocyclisation approach based on the double aromatic nucleophilic substitution (SNACK) was developed. This methodology allows a facile incorporation of heterocyclic motifs into macrocyclic rings and rapid synthesis of a significant number of structurally diverse macrocycles. SNACK macrocyclisation enables preparation of stable diastereoisomers of conformationally restricted macrocycles (atropisomers). Practical application of SNACK macrocyclisation in a drug discovery project was exemplified by the identification of high affinity macrocyclic binders of B-cell lymphoma 6 (BCL6).
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.
Piperazine substituted 1, 3 - di-substituted urea compound and piperazine substituted amide compounds and a method for its preparation and use
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Paragraph 0450-0452, (2017/04/22)
The present invention relates to a class of piperazine substituted 1,3-disubstitued urea compounds and piperazine substituted amide compounds, or pharmaceutically acceptable salts of the piperazine substituted 1,3-disubstitued urea compounds and the piper
The discovery and optimization of novel dual inhibitors of topoisomerase ii and histone deacetylase
Zhang, Xuan,Bao, Bin,Yu, Xiuhua,Tong, Linjiang,Luo, Yu,Huang, Qingqing,Su, Mingbo,Sheng, Li,Li, Jia,Zhu, Hong,Yang, Bo,Zhang, Xiongwen,Chen, Yi,Lu, Wei
, p. 6981 - 6995 (2013/11/06)
A novel class of podophyllotoxin derivatives have been designed and synthesized based on the synergistic antitumor effects of topoisomerase II and histone deacetylase inhibitors. Their inhibitory activities towards histone deacetylases and Topo II and their cytotoxicities in cancer cell lines were evaluated. The aromatic capping group connection, linker length and zinc-binding group were systematically varied and preliminary conclusions regarding structure-activity relationships are discussed. Among all of the synthesized hybrid compounds, compound 24d showed the most potent HDAC inhibitory activity at a low nanomolar level and exhibited powerful antiproliferative activity towards HCT116 colon carcinoma cells at a low micromolar level. Further exploration of this series led to the discovery of potent dual inhibitor 32, which exhibited the strongest in vitro cytotoxic activity.
Incorporation of piperazino functionality into 1,3-disubstituted urea as the tertiary pharmacophore affording potent inhibitors of soluble epoxide hydrolase with improved pharmacokinetic properties
Huang, Shao-Xu,Li, Hui-Yuan,Liu, Jun-Yan,Morisseau, Christophe,Hammock, Bruce D.,Long, Ya-Qiu
supporting information; experimental part, p. 8376 - 8386 (2011/02/21)
The inhibition of the mammalian soluble epoxide hydrolase (sEH) is a promising new therapy in the treatment of hypertension, inflammation, and other disorders. However, the problems of limited water solubility, high melting point, and low metabolic stabil
