Abstract
Isopropyl- and fluoroisopropyl-amino derivatives of the β(1)-adrenergic receptor antagonist 2-[4-[3-(tert-butyl-amino)-2-hydroxypropoxy]phenyl]-3-methyl-6-methoxy-4(3H)-quinazolinone ((±)HX-CH 44) were synthesized, including a concise and efficient preparation of the core, 2-(4-hydroxyphenyl)-6-methoxy-3-methylquinazolin-4(3H)-one. In vitro binding assays showed that the fluorinated analog was selective towards β(1)-adrenergic receptors over β(2)-adrenergic and 5-HT(1A) receptors. An X-ray crystallographic characterization of the fluorinated analog is also reported.
Copyright © 2011 Elsevier Ltd. All rights reserved.
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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Adrenergic beta-1 Receptor Agonists / chemical synthesis*
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Adrenergic beta-1 Receptor Agonists / chemistry
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Adrenergic beta-1 Receptor Agonists / pharmacology*
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Chemistry Techniques, Synthetic
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Humans
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Models, Molecular
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Molecular Structure
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Propanolamines / chemical synthesis
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Propanolamines / chemistry
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Propanolamines / pharmacology*
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Quinazolinones / chemical synthesis
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Quinazolinones / chemistry
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Quinazolinones / pharmacology*
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Receptors, Adrenergic, beta-1 / metabolism*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Adrenergic beta-1 Receptor Agonists
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Propanolamines
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Quinazolinones
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Receptors, Adrenergic, beta-1
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HX-CH 44BS