Abstract
Utilizing a combination of high-throughput and multi-step synthesis, SAR in a novel series of M(1) acetylcholine receptor antagonists was rapidly established. The efforts led to the discovery the highly potent M(1) antagonists 6 (VU0431263), and 8f (VU0433670). Functional Schild analysis and radioligand displacement experiments demonstrated the competitive, orthosteric binding of these compounds; human selectivity data are presented.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Acetylcholine / metabolism
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Amides / chemical synthesis
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Amides / chemistry*
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Amides / pharmacology
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Animals
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Binding, Competitive / drug effects
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CHO Cells
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Cricetinae
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Cricetulus
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Humans
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / pharmacology
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Receptor, Muscarinic M1 / antagonists & inhibitors*
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Receptor, Muscarinic M1 / genetics
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Receptor, Muscarinic M1 / metabolism
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Stereoisomerism
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Stilbenes / chemical synthesis*
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Stilbenes / chemistry
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Stilbenes / pharmacology
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Structure-Activity Relationship
Substances
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Amides
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Piperazines
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Receptor, Muscarinic M1
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Stilbenes
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VU0431263
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VU0433670
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Acetylcholine