202823-67-4Relevant articles and documents
Bridged Ring compounds As Hepatitis C Virus (HCV) Inhibitors And Pharmaceutical Applications Thereof
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Paragraph 0979; 1000; 1001; 1002; 1003, (2015/03/28)
Provided herein is a compound having Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are pharmaceutical compositions comprising the compounds disclosed herein, which can be used for treating HCV infection or a HCV disorder.
BRIDGED RING COMPOUNDS AS HEPATITIS C VIRUS (HCV) INHIBITORS AND PHARMACEUTICAL APPLICATIONS THEREOF
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Paragraph 00417, (2014/02/16)
Provided herein is a compound having Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are pharmaceutical compositions comprising the compounds disclosed herein, which can be used for treating HCV infection or a HCV disorder.
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
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.
, p. 1367 - 1383 (2007/10/03)
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.
Synthesis and biological evaluation of 3-heterocyclyl-7,8,9,10-tetrahydro- (7,10-ethano)-1,2,4-triazolo[3,4-a]phthalazines and analogues as subtype-selective inverse agonists for the GABAAα5 benzodiazepine binding site
Street, Leslie J.,Sternfeld, Francine,Jelley, Richard A.,Reeve, Austin J.,Carling, Robert W.,Moore, Kevin W.,McKernan, Ruth M.,Sohal, Bindi,Cook, Susan,Pike, Andrew,Dawson, Gerard R.,Bromidge, Frances A.,Wafford, Keith A.,Seabrook, Guy R.,Thompson, Sally A.,Marshall, George,Pillai, Goplan V.,Castro, José L.,Atack, John R.,MacLeod, Angus M.
, p. 3642 - 3657 (2007/10/03)
The identification of a novel series of 7,8,9,10-tetrahydro-(7,10-ethano)- 1,2,4-triazolo[3,4-a]phthalazines as GABAAα5 inverse agonists, which have both binding and functional (efficacy) selectivity for the benzodiazepine binding site of α5- over α1-, α2-, and α3-containing GABAA receptor subtypes, is described. Binding selectivity was determined to a large part by the degree of planarity of the fused ring system whereas functional selectivity was dependent on the nature of the heterocycle at the 3-position of the triazolopyridazine ring. 3-Furan and 5-methylisoxazole were shown to be optimal for GABAAα5 functional selectvity. 3-(5-Methylisoxazol-3-yl)-6-(2-pyridyl)methyloxy-1,2,4- triazolo[3,4-a]phthalazine (43) was identified as a full inverse agonist at the GABAAα5 subtype with functional selectivity over the other GABAA receptor subtypes and good oral bioavailability.
