210890-95-2Relevant academic research and scientific papers
Identification and structure-activity relationship of 8-hydroxy-quinoline-7-carboxylic acid derivatives as inhibitors of Pim-1 kinase
Sliman, Faten,Blairvacq, Mélina,Durieu, Emilie,Meijer, Laurent,Rodrigo, Jordi,Desma?le, Didier
scheme or table, p. 2801 - 2805 (2010/07/05)
Pim-1 kinase is a cytoplasmic serine/threonine kinase that controls programmed cell death by phosphorylating substrates that regulate both apotosis and cellular metabolism. A series of 2-styrylquinolines and quinoline-2-carboxamides has been identified as potent inhibitors of the Pim-1 kinase. The 8-hydroxy-quinoline 7-carboxylic acid moiety appeared to be a crucial pharmacophore for activity. Molecular modeling indicated that interaction of this scaffold with Asp186 and Lys67 residues within the ATP-binding pocket might be responsible for the kinase inhibitory potency.
Quinoline derivatives, having in particular antiviral properties, preparation and biological applications thereof
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Page column 11, (2008/06/13)
The invention concerns quinoline derivatives of formula (I) in which: Ra, Rband Rc, identical or different represent one or several substituents, themselves identical or different, in any position on the cycles, this or th
Styrylquinoline derivatives: A new class of potent HIV-1 integrase inhibitors that block HIV-1 replication in CEM cells
Mekouar, Khalid,Mouscadet, Jean-Fran?ois,Desma?le, Didier,Subra, Frédéric,Leh, Hervé,Savouré, Delphine,Auclair, Christian,D'Angelo, Jean
, p. 2846 - 2857 (2007/10/03)
On the basis of the fact that several polynucleotidyl transferases, related to HIV integrase, contain in their active site two divalent metal cations, separated by ca. 4 ?, new potential HIV integrase inhibitors were designed, in which a quinoline substructure is linked to an aryl nucleus possessing various hydroxy substitution patterns, by means of an ethylenic spacer. Although the most active compounds contain the catechol structure, this group is not essential for the activity, since compound 21 that lacks such a moiety is a potent drug, implicating the presence of a different pharmacophore. The most promising styrylquinolines thus synthesized inhibit HIV-1 integrase in vitro at micromolar or submicromolar concentrations and block HIV replication in CEM cells, with no significant cellular toxicity in a 5-day period assay. These inhibitors are active against integrase core domain-mediated disintegration, suggesting that fragment 50-212 is their actual target. These new styrylquinolines may provide lead compounds for the development of novel antiretroviral agents for AIDS therapeutics, based upon inhibition of HIV integrase. They might also be used in the elucidation of the mechanism of inhibition of this enzyme; e.g., they could serve as candidates for cocrystallization studies with HIV integrase.
