- SUBSTITUTED HETEROAROMATIC PYRAZOLO-PYRIDINES AND THEIR USE AS GLUN2B RECEPTOR MODULATORS
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Substituted Pyrazolo-pyridines as GluN2B receptor ligands. Such compounds may be used in GluN2B receptor modulation and in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by GluN2B receptor activity.
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Page/Page column 68; 70
(2020/12/30)
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- Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4- triazolo[3,4-a]phthalazines as GABAA receptor agonists at the α3 subunit
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We have previously identified the 7,8,9,10-tetrahydro-7,10-ethano-1,2,4- triazolo[3,4-a]phthalazine (1) as a potent partial agonist for the 0.3 receptor subtype with 5-fold selectivity in binding affinity over α1. This paper describes a detailed investigation of the substituents on this core structure at both the 3- and 6-positions. Despite evaluating a wide range of groups, the maximum selectivity that could be achieved in terms of affinity for the α3 subtype over the α1 subtype was 12-fold (for 57). Although most analogues showed no selectivity in terms of efficacy, some did show partial agonism at α1 and antagonism at α3 (e.g., 25 and 75). However, two analogues tested (93 and 96), both with triazole substituents in the 6-position, showed significantly higher efficacy for the α3 subtype over the α1 subtype. This was the first indication that selectivity in efficacy in the required direction could be achieved in this series.
- Russell, Michael G. N.,Carling, Robert W.,Atack, John R.,Bromidge, Frances A.,Cook, Susan M.,Hunt, Peter,Isted, Catherine,Lucas, Matt,McKernan, Ruth M.,Mitchinson, Andrew,Moore, Kevin W.,Narquizian, Robert,Macaulay, Alison J.,Thomas, David,Thompson, Sally-Anne,Wafford, Keith A.,Castro, José L.
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p. 1367 - 1383
(2007/10/03)
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- Electroorganic synthesis of 2,5-dialkoxydihydrofurans and pyridazines on solid phase using polymer beads as supports
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Electroorganic synthesis has defied application in Solid-Phase Organic Synthesis (SPOS) so far. Typically more than 99.9% of the substrate molecules immobilized on a polymeric support are buried in the interior of the bead, and therefore are unable to undergo direct contact with a heterogeneous reagent such as an electrode. This intrinsic impediment for an electrochemical reaction can be overcome by the use of a redox mediator which shuttles electrons from the electrode to the polymer bound substrate molecules. This approach of indirect electroorganic synthesis was successfully applied for the 2,5-dialkoxylation of furans on solid phase. The oxidation products can be hydrolyzed and through condensation with hydrazine hydrate substituted pyridazines are produced in 50-65% overall yield. Georg Thieme Verlag Stuttgart.
- Nad, Sukanya,Breinbauer, Rolf
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p. 3654 - 3665
(2007/10/03)
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