Abstract
A series of N-substituted 3-(4-piperidinyl)-1,3-benzoxazolinones and oxindoles are reported which were found to be potent and selective muscarinic M1 agonists. By control of the physicochemical characteristics of the series, particularly the lipophilicity, compounds with good metabolic stability and excellent brain penetration were identified. An exemplar of the series was shown to be pro-cognitive in the novel object recognition rat model of temporal induced memory deficit.
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Benzoxazoles / chemistry
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Benzoxazoles / pharmacokinetics*
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Benzoxazoles / therapeutic use
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Brain / metabolism
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Indoles / chemistry
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Indoles / pharmacokinetics*
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Indoles / therapeutic use
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Memory Disorders / drug therapy*
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Muscarinic Agonists / chemistry
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Muscarinic Agonists / pharmacokinetics*
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Muscarinic Agonists / therapeutic use
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Nootropic Agents / chemistry
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Nootropic Agents / pharmacokinetics*
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Nootropic Agents / therapeutic use
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Oxindoles
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Rats
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Receptor, Muscarinic M1 / metabolism*
Substances
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Benzoxazoles
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Indoles
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Muscarinic Agonists
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Nootropic Agents
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Oxindoles
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Receptor, Muscarinic M1
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2-oxindole
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benzoxazolone