219786-51-3Relevant academic research and scientific papers
Detailed Exploration around 4-Aminoquinolines Chemical Space to Navigate the Lysine Methyltransferase G9a and DNA Methyltransferase Biological Spaces
Rabal, Obdulia,Sánchez-Arias, Juan Antonio,José-Enériz, Edurne San,Agirre, Xabier,De Miguel, Irene,Garate, Leire,Miranda, Estibaliz,Sáez, Elena,Roa, Sergio,Martínez-Climent, José Angel,Liu, Yingying,Wu, Wei,Xu, Musheng,Prosper, Felipe,Oyarzabal, Julen
, p. 6546 - 6573 (2018/06/25)
Epigenetic regulators that exhibit aberrant enzymatic activities or expression profiles are potential therapeutic targets for cancers. Specifically, enzymes responsible for methylation at histone-3 lysine-9 (like G9a) and aberrant DNA hypermethylation (DNMTs) have been implicated in a number of cancers. Recently, molecules bearing a 4-aminoquinoline scaffold were reported as dual inhibitors of these targets and showed a significant in vivo efficacy in animal models of hematological malignancies. Here, we report a detailed exploration around three growing vectors born by this chemotype. Exploring this chemical space led to the identification of features to navigate G9a and DNMT1 biological spaces: not only their corresponding exclusive areas, selective compounds, but also common spaces. Thus, we identified from selective G9a and first-in-class DNMT1 inhibitors, >1 log unit between their IC50 values, with IC50 50 50 nM for both targets (e.g., 13). Their ADME/Tox profiling and antiproliferative efficacies, versus some cancer cell lines, are also reported.
Structure-activity relationship investigation of Phe-Arg mimetic region of human glutaminyl cyclase inhibitors
Ngo, Van T.H.,Hoang, Van-Hai,Tran, Phuong-Thao,Van Manh, Nguyen,Ann, Jihyae,Kim, Eunhye,Cui, Minghua,Choi, Sun,Lee, Jiyoun,Kim, Hee,Ha, Hee-Jin,Choi, Kwanghyun,Kim, Young-Ho,Lee, Jeewoo
, p. 3133 - 3144 (2018/05/23)
Glutamyl cyclase (QC) is a promising therapeutic target because of its involvement in the pathogenesis of Alzheimer's disease. In this study, we developed novel QC inhibitors that contain 3-aminoalkyloxy-4-methoxyphenyl and 4-aminoalkyloxyphenyl groups to replace the previously developed pharmacophore. Several potent inhibitors were identified, showing IC50 values in a low nanomolar range, and were further studied for in vitro toxicity and in vivo activity. Among these, inhibitors 51 and 53 displayed the most potent AβN3pE?40-lowering effects in in vivo acute model with reasonable BBB penetration, without showing cytotoxicity and hERG inhibition. The molecular modeling analysis of 53 indicated that the salt bridge interaction and the hydrogen bonding in the active site provided a high potency. Given the potent activity and favorable BBB penetration with low cytotoxicity, we believe that compound 53 may serve as a potential candidate for anti-Alzheimer's agents.
Substituted benzanilides as CCR5 receptors ligands, antiinflammatory agents and antiviral agents
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, (2008/06/13)
This invention relates to substituted benzanilides which are ligands, agonists or antagonists, of the CCR5 receptor. In addition, this invention relates to the treatment and prevention of disease states mediated by CCR5, including, but not limited to, ast
