Synthesis and preliminary pharmacological activity of aminoalkoxy isosteres of glycolate ester anticholinergics.
A sides of 2-(N-substituted amino)alkoxy-1,1-diphenylethanols was synthesized and evaluated for anticholinergic activity. The compounds differ structurally from the glycolate ester-type anticholinergic compounds by the bioisosteric substitution of a methylene group for the ester carbonyl moiety. The ethers which result from this change have increased lipophilicity compared to their ability to inhibit perphenazine-induced catatonia in rats. Structure-activity relationships of the compounds are discussed.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002389:Catatonia / Q000139:chemically induced / Q000503:physiopathology; D002626:Chemistry, Pharmaceutical; D006016:Glycolates / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010276:Parasympatholytics / Q000138:chemical synthesis*; D010546:Perphenazine / Q000037:antagonists & inhibitors; D011817:Rabbits; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship
D006016:Glycolates; D010276:Parasympatholytics; D010546:Perphenazine