Abstract
We have previously described a series of antagonists that showed high potency and selectivity for the NK(1) receptor. However, these compounds also had the undesirable property of existing as a mixture of interconverting rotational isomers. Here we show that alteration of the 2-naphthyl substituent can modulate the rate of isomer exchange. Comparisons of the NK(1) receptor affinity for the various conformational forms has facilitated the development of a detailed NK(1) pharmacophore model.
MeSH terms
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Animals
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Biological Availability
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Brain / metabolism
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Cell Line, Tumor
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Dogs
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Gerbillinae
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Humans
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In Vitro Techniques
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Magnetic Resonance Spectroscopy
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Mice
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Models, Molecular
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Naphthalenes / chemical synthesis*
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Naphthalenes / chemistry
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Naphthalenes / pharmacology
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Neurokinin-1 Receptor Antagonists*
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Pulmonary Artery / drug effects
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Pulmonary Artery / metabolism
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Rabbits
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Radioligand Assay
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Receptors, Neurokinin-1 / chemistry
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Receptors, Neurokinin-1 / metabolism
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Naphthalenes
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Neurokinin-1 Receptor Antagonists
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Receptors, Neurokinin-1