955359-96-3Relevant academic research and scientific papers
The discovery of quinoline based single-ligand human H1and H3receptor antagonists
Procopiou, Panayiotis A.,Ancliff, Rachael A.,Gore, Paul M.,Hancock, Ashley P.,Hodgson, Simon T.,Holmes, Duncan S.,Keeling, Steven P.,Looker, Brian E.,Parr, Nigel A.,Rowedder, James E.,Slack, Robert J.
, p. 5855 - 5859 (2016/12/06)
A novel series of potent quinoline-based human H1and H3bivalent histamine receptor antagonists, suitable for intranasal administration for the potential treatment of allergic rhinitis associated nasal congestion, were identified. Com
Optimization of 5-pyridazin-3-one phenoxypropylamines as potent, selective histamine H3 receptor antagonists with potent cognition enhancing activity
Tao, Ming,Aimone, Lisa D.,Huang, Zeqi,Mathiasen, Joanne,Raddatz, Rita,Lyons, Jacquelyn,Hudkins, Robert L.
experimental part, p. 414 - 423 (2012/03/11)
Previous studies have shown that (5-{4-[3-(R)-2-methylpyrrolin-1-yl- propoxy]phenyl}-2H-pyridazin-3-one) 2 had high affinity for both the human (hH3R Ki = 2.8 nM) and rat H3Rs (rH 3R Ki = 8.5 nM) but displayed low oral bioavailability in the rat. Optimization of the 5-pyridazin-3-one R2 and R6 positions to improve the pharmacokinetic properties over 2 led to the identification of 5-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2-pyridin- 2-yl-2H-pyridazin-3-one 29. Compound 29 displayed high affinity for both human and rat H3Rs (hH3R Ki = 1.7 nM, rH3R Ki = 3.7 nM) with a greater than 1000-fold selectivity over the other histamine receptor subtypes and favorable pharmacokinetic properties across species (F = 78% rat, 92% dog, 96% monkey). It showed low binding to human plasma proteins, weakly inhibited cytochrome P450 isoforms, and displayed an excellent safety profile for a CNS-active compound. 29 displayed potent H3R antagonist activity in the brain in a rat dipsogenia model and demonstrated enhancement of cognitive function in a rat social recognition model at low doses. However, the development of compound 29 was discontinued because of genotoxicity.
QU1NOLINE DERIVATIVES AND THEIR USES FOR RHINITIS AND URTICARIA
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Page/Page column 52, (2010/09/17)
The present invention relates to compounds of formula (I) and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various diseases, such as allergic rhinitis.
Pyridizinone derivatives
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Page/Page column 67, (2008/06/13)
The present invention provides compounds of formula (I*): their use as H3 inhibitors, processes for their preparation, and pharmaceutical compositions thereof.
2-SUBSTITUTED 4-BENZYLPHTHALAZINONE DERIVATIVES AS HISTAMINE H1 AND H3 ANTAGONISTS
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Page/Page column 71, (2008/06/13)
The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various disorders, such as allergic rhinitis.
HISTAMINE RECEPTOR ANTAGONISTS COMPRISING AN AZEPIN CORE
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Page/Page column 43, (2008/06/13)
The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various disorders, such as allergic rhinitis.
