Abstract
This Letter describes the synthesis and SAR, developed through an iterative analogue library approach, of a novel series of selective M1 mAChR antagonists for the potential treatment of Parkinson's disease, dystonia and other movement disorders. Compounds in this series possess M1 antagonist IC(50)s in the 441nM-19microM range with 8- to >340-fold functional selectivity versus rM2-rM5.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Combinatorial Chemistry Techniques
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Dose-Response Relationship, Drug
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Dystonia / drug therapy
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Heterocyclic Compounds / chemical synthesis*
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Heterocyclic Compounds / chemistry
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Heterocyclic Compounds / pharmacokinetics
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Heterocyclic Compounds / pharmacology*
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Humans
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Molecular Structure
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Muscarinic Antagonists / chemical synthesis*
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Muscarinic Antagonists / chemistry
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Muscarinic Antagonists / pharmacokinetics
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Muscarinic Antagonists / pharmacology*
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Parkinson Disease / drug therapy
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Receptor, Muscarinic M1 / metabolism*
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Receptors, G-Protein-Coupled / metabolism*
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Receptors, Muscarinic / metabolism*
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Structure-Activity Relationship
Substances
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Heterocyclic Compounds
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Muscarinic Antagonists
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Receptor, Muscarinic M1
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Receptors, G-Protein-Coupled
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Receptors, Muscarinic