Abstract
The synthesis of unsymmetrical naphth[2,3-d]imidazolium and bridged naphth[2,3-d]imidazolium derivatives and their substance P (SP) antagonist activity are described. All compounds were evaluated for their ability to displace SP from neurokinin-1 (NK-1) receptor sites using standard receptor binding methodology (rat forebrain membrane). 1,3-Diethyl-2-[3-(1,3-dihydro-1,3,3-timethyl-2H-indol-2-ylidene) -1-propenyl]-1H-naphth[2,3-d]imidazolium chloride (7a), a representative compound in this series, was further evaluated for SP antagonist activity in a guinea pig ileum contractility assay. In vivo SP antagonist activity of 7a was demonstrated using SP-induced salivation and paw edema models performed in rats.
MeSH terms
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Animals
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Binding, Competitive
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Edema / chemically induced
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Edema / prevention & control
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Female
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Guinea Pigs
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Ileum / physiology
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Imidazoles / chemical synthesis*
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Imidazoles / metabolism
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Imidazoles / pharmacology
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Indoles / chemical synthesis*
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Indoles / metabolism
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Indoles / pharmacology
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Male
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Molecular Structure
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Muscle Contraction / drug effects
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Rats
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Rats, Inbred Strains
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Receptors, Neurokinin-2
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Receptors, Neurotransmitter / metabolism
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Salivation / drug effects
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Structure-Activity Relationship
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Substance P / antagonists & inhibitors*
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Substance P / metabolism
Substances
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Imidazoles
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Indoles
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Receptors, Neurokinin-2
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Receptors, Neurotransmitter
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1,3-diethyl-2-(3-(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)-1-propenyl)-1H-naphth(2,3-d)imidazolium
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Substance P