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 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.
D000818:Animals; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D004983:Ethanolamines / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D010276:Parasympatholytics / Q000138:chemical synthesis*; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
D004952:Esters; D004983:Ethanolamines; D007202:Indicators and Reagents; D010276:Parasympatholytics; D010666:Phenylpropionates; D011976:Receptors, Muscarinic