Identification of pyridazin-3-one derivatives as potent, selective histamine H3 receptor inverse agonists with robust wake activity
摘要:
H3R structure-activity relationships on a novel class of pyridazin-3-one H3R antagonists/inverse agonists are disclosed. Modifications of the pyridazinone core, central phenyl ring and linker led to the identification of molecules with excellent target potency, selectivity and pharmacokinetic properties. Compounds 13 and 21 displayed potent functional H3R antagonism in vivo in the rat dipsogenia model and demonstrated robust wake activity in the rat EEG/EMG model. (C) 2011 Elsevier Ltd. All rights reserved.
Identification of pyridazin-3-one derivatives as potent, selective histamine H3 receptor inverse agonists with robust wake activity
摘要:
H3R structure-activity relationships on a novel class of pyridazin-3-one H3R antagonists/inverse agonists are disclosed. Modifications of the pyridazinone core, central phenyl ring and linker led to the identification of molecules with excellent target potency, selectivity and pharmacokinetic properties. Compounds 13 and 21 displayed potent functional H3R antagonism in vivo in the rat dipsogenia model and demonstrated robust wake activity in the rat EEG/EMG model. (C) 2011 Elsevier Ltd. All rights reserved.
The present invention provides compounds of formula (I*):
their use as H
3
inhibitors, processes for their preparation, and pharmaceutical compositions thereof.
本发明提供了式(I*)的化合物:它们作为H3抑制剂的用途,其制备方法以及药物组合物。
Pyridazinone Derivatives
申请人:Bacon Edward R.
公开号:US20110288075A1
公开(公告)日:2011-11-24
The present invention is directed to novel pyridazinone derivatives that mediate enzymatic activity. In particular, the compounds may be effective in the treatment of diseases or disease states related to the activity of the histamine H3 receptor, including, for example, neurodegenerative disorders, sleep/wake disorders, attention deficit hyperactivity disorder and cognition/cognitive disorders.
The present invention is directed to novel pyridazinone derivatives that mediate enzymatic activity. In particular, the compounds may be effective in the treatment of diseases or disease states related to the activity of the histamine H3 receptor, including, for example, neurodegenerative disorders, sleep/wake disorders, attention deficit hyperactivity disorder and cognition.
Aryl pyridazinone derivatives and their use as H3 receptor ligands
申请人:Bacon Edward R.
公开号:US08586588B2
公开(公告)日:2013-11-19
The present invention is directed to novel pyridazinone derivatives that mediate enzymatic activity. In particular, the compounds and/or their pharmaceutically acceptable salts may be effective in the treatment of diseases or disease states related to the activity of the histamine H3 receptor, including, for example, neurodegenerative disorders, sleep/wake disorders, attention deficit hyperactivity disorder and cognition/cognitive disorders.
The present invention provides compounds of formula (I*):
their use as H3 inhibitors, processes for their preparation, and pharmaceutical compositions thereof.