16135-41-4Relevant academic research and scientific papers
New MT2 melatonin receptor-selective ligands: Agonists and partial agonists
Boutin, Jean A.,Bonnaud, Anne,Brasseur, Chantal,Bruno, Olivier,Lepretre, Nolwenn,Oosting, Peter,Coumailleau, Sophie,Delagrange, Philippe,Nosjean, Olivier,Legros, Céline
, (2017/07/04)
The search for melatonin receptor agonists and antagonists specific towards one of the receptor subtypes will extend our understanding of the role of this system in relaying circadian information to the body. A series of compounds derived from a hit compound discovered in a screening process led to powerful agonists specific for one of the isoform of the melatonin receptor namely, MT2. The compounds are based on a poorly explored skeleton in the molecular pharmacology of melatonin. By changing the steric hindrance of one substituent (i.e., from a hydrogen atom to a tributylstannyl group), we identified a possible partial agonist that could lead to antagonist analogues. The functionalities of these compounds were measured with a series of assays, including the binding of GTPγS, the inhibition of the cyclic AMP production, the β-arrestin recruitment, and the cell shape changes as determined by cellular dielectric spectroscopy (CellKey). The variations between the compounds are discussed.
Synthesis and biological evaluation of new carbohydrate-substituted indenoisoquinoline topoisomerase I inhibitors and improved syntheses of the experimental anticancer agents indotecan (LMP400) and indimitecan (LMP776)
Beck, Daniel E.,Agama, Keli,Marchand, Christophe,Chergui, Adel,Pommier, Yves,Cushman, Mark
, p. 1495 - 1512 (2014/03/21)
Carbohydrate moieties were strategically transported from the indolocarbazole topoisomerase I (Top1) inhibitor class to the indenoisoquinoline system in search of structurally novel and potent Top1 inhibitors. The syntheses and biological evaluation of 20 new indenoisoquinolines glycosylated with linear and cyclic sugar moieties are reported. Aromatic ring substitution with 2,3-dimethoxy-8,9-methylenedioxy or 3-nitro groups exerted strong effects on antiproliferative and Top1 inhibitory activities. While the length of the carbohydrate side chain clearly correlated with antiproliferative activity, the relationship between stereochemistry and biological activity was less clearly defined. Twelve of the new indenoisoquinolines exhibit Top1 inhibitory activity equal to or better than that of camptothecin. An advanced synthetic intermediate from this study was also used to efficiently prepare indotecan (LMP400) and indimitecan (LMP776), two anticancer agents currently under investigation in a Phase I clinical trial at the National Institutes of Health.
Cyclic nucleotide phosphodiesterase inhibitors, preparation and uses thereof
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Page/Page column 16-17, (2010/02/08)
The invention concerns novel benzodiazepine derivatives and their uses in the field of therapeutics particularly for treating pathologies involving the activity of a cyclic nucleotide phosphodiesterase. It also concerns methods for preparing them and novel synthesis intermediates. The inventive compounds more particularly correspond to general formula (I):
Preparation of Novel 4-Substituted 6-Methoxy, 6,7-Dimethoxy-, and 6,7-(Methylenedioxy)isochroman-3-ones. 2
Khanapure, Subhash P.,Biehl, Edward R.
, p. 1471 - 1475 (2007/10/02)
The title compounds 20, 21, and 22 have been prepared in modest yields by a two-step reaction involving first the reaction of bromoarenes 3, 7, and 8 with lithioalkyl- and lithioarylacetonitriles under aryne-forming conditions.The cyano products 10, 14, and 16 so formed were then converted to the corresponding isochroman-3-ones by acidic hydrolysis.
STUDIES ON THE SYNTHESIS OF BENZOLACTAM RINGS. II SYNTHESIS OF 1,4-DIHYDRO-3(2H)-ISOQUINOLINONE DERIVATIVES
Kamochi, Yasuko,Watanabe, Yasuo
, p. 2385 - 2391 (2007/10/02)
A new synthesis of 1,4-dihydro-3(2H)-isoquinolinones by the amidomethylation with acrylacetamide or acrylacetonitrile and paraformaldehyde in some acid-catalysts is described.
