Molecular modification of anticholinergics as probes for muscarinic receptors. 2. Amino esters of .alpha.-methyltropic acid

As a continuation of our goals to study molecular probes for muscarinic cholinergic receptors, a series of 3-substituted 2-methyl-2-phenylpropanoates with the general structure of C6H5C(CH2X)(CH3)COOCH2CH2NEt2 where X = OH, OTs, F, Cl, Br, I, and OAc were prepared and their antispasmodic activities...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1987-02, Vol.30 (2), p.424-427
Main Authors: Lu, Matthias C, Shih, Lisa B, Jae, Hwan S, Gearien, James E, Thompson, Emmanual B
Format: Article
Language:English
Subjects:
Animals
Esters - chemical synthesis
Esters - pharmacology
Ethanolamines - chemical synthesis
Ethanolamines - pharmacology
In Vitro Techniques
Indicators and Reagents
Magnetic Resonance Spectroscopy
Male
Mass Spectrometry
Muscle Contraction - drug effects
Muscle, Smooth - physiology
Parasympatholytics - chemical synthesis
Phenylpropionates - chemical synthesis
Phenylpropionates - pharmacology
Rats
Rats, Inbred Strains
Receptors, Muscarinic - drug effects
Receptors, Muscarinic - metabolism
Structure-Activity Relationship
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Summary:As a continuation of our goals to study molecular probes for muscarinic cholinergic receptors, a series of 3-substituted 2-methyl-2-phenylpropanoates with the general structure of C6H5C(CH2X)(CH3)COOCH2CH2NEt2 where X = OH, OTs, F, Cl, Br, I, and OAc were prepared and their antispasmodic activities examined on isolated rat ileum preparations. Structure-activity relationship studies with these compounds provide further evidence suggesting that binding of an aromatic moiety in a specific location within the hydrophobic region of the receptor is important for anticholinergic potency. A nucleophilic displacement of chloride by "naked" fluoride under mild conditions is also reported.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00385a028