Abstract
A series of 2-(acyl)amino-8-substituted-2,8-diazaspiro[4,5]decan-1,3-diones (5a-j), structurally related to the muscarinic agonist RS-86, was synthesized and compounds tested for their affinity towards muscarinic receptors. Though all compounds proved to be less active than the model in binding studies, only three derivatives (5a, b, c) being able to significantly displace 3H-QNB at mM concentration, their behaviour could be interpreted in terms of theoretical molecular descriptors computed on the basis of the suggestions coming from Molecular Dynamics simulations of ligand-receptor complexes.
MeSH terms
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Animals
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Carbachol / chemistry
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Cerebral Cortex / metabolism
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Computer Simulation
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Models, Molecular
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Muscarinic Agonists / chemical synthesis*
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Muscarinic Agonists / chemistry
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Muscarinic Agonists / pharmacology
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Protein Conformation*
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Quinuclidinyl Benzilate / pharmacology
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Rats
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Receptors, Muscarinic / chemistry
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Receptors, Muscarinic / drug effects
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Spiro Compounds / chemical synthesis*
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Spiro Compounds / chemistry
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Spiro Compounds / pharmacology
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Succinimides / chemical synthesis*
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Succinimides / chemistry
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Succinimides / pharmacology
Substances
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Muscarinic Agonists
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Receptors, Muscarinic
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Spiro Compounds
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Succinimides
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Quinuclidinyl Benzilate
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Carbachol