Abstract
The synthesis of oximeethers of 2,3-dihydro-1,8-naphthyridine and 2, 3-dihydrothiopyrano[2,3-b]pyridine is described. These compounds exhibit a selective beta-blocking activity, with a selectivity towards beta(2)-receptors. Groups in the N(1) position giving rise to a considerable steric hindrance led to a higher beta(2)-blocking selectivity, whereas groups creating a moderate hindrance caused a weak but significant decrease in beta(2)-antagonist potency. Substitution of the N(1)-R group with a sulfur atom led to compounds possessing beta(1)-, beta(2)- and beta(3)-blocking properties. Compounds 9c(1) and 10a(1) showed a beta(3)-antagonist activity slightly lower than that of propranolol.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipose Tissue / drug effects
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Adrenergic beta-Antagonists / chemical synthesis*
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Adrenergic beta-Antagonists / pharmacology
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Animals
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Antihypertensive Agents / chemical synthesis*
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Antihypertensive Agents / metabolism
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Antihypertensive Agents / pharmacology*
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Drug Evaluation, Preclinical
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Guinea Pigs
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Inhibitory Concentration 50
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Isoproterenol / pharmacology
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Male
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Naphthyridines / chemistry*
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Pyrans / chemical synthesis*
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Pyrans / pharmacology
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Pyridines / chemical synthesis*
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Pyridines / pharmacology
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Rats
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Rats, Wistar
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Receptors, Adrenergic, beta-1 / drug effects
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Receptors, Adrenergic, beta-2 / drug effects
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Receptors, Adrenergic, beta-3 / drug effects
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Structure-Activity Relationship
Substances
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2,3-dihydro-1,8-naphthyridine
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2,3-dihydrothiopyran(2,3-b)pyridine
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Adrenergic beta-Antagonists
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Antihypertensive Agents
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Naphthyridines
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Pyrans
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Pyridines
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Receptors, Adrenergic, beta-1
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Receptors, Adrenergic, beta-2
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Receptors, Adrenergic, beta-3
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Isoproterenol