Abstract
A novel series of 4-pyridazin-3-one and 5-pyridazin-3-one analogues were designed and synthesized as H(3)R antagonists. Structure-activity relationship revealed the 5-pyridazin-3-ones 8a and S-methyl 8b had excellent human and rat H(3)R affinities, and acceptable pharmacokinetic properties. In vivo evaluation of 8a showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG/EMG model.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Histamine Antagonists / chemical synthesis*
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Histamine Antagonists / chemistry
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Histamine Antagonists / pharmacology*
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Humans
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Male
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Molecular Sequence Data
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Molecular Structure
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Propylamines / chemical synthesis
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Propylamines / chemistry
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Propylamines / pharmacology*
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Pyridazines / chemical synthesis
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Pyridazines / chemistry
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Pyridazines / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Receptors, Histamine H3 / metabolism*
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Structure-Activity Relationship
Substances
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4-pyridazin-3-one phenoxypropylamine
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5-pyridazin-3-one phenoxypropylamine
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Histamine Antagonists
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Propylamines
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Pyridazines
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Receptors, Histamine H3