Studies on the Structure‐action Relationships of the Choline Group

It is well known that the ester group contributes in some important but unknown way to the intense physiological activity of acetylcholine (I), and consequently the effects of changing this unit of structure are of considerable interest in any study of the structure-action relationships of the choline group.Among the simpler changes possible are : (i) replacement of the carbonyl (C= 0) group by methylene as in choline ethyl ether (II); (ii) replacement of the linking 0-atom of the ester group by methylene as in 4-keto-amyltrimethylammonium (III); and (iii) replacement of both the carbonyl group and the linking 0-atom by methylene groups as in n-amyl- trimethylammonium (IV).Compounds II and IV have been known for many years choline on rabbit auricles in the presence and in the absence of eserine.Serial Nos.* The senior author (H.R.I.) regrets that the paper by Alles and Knoefel (1939) was unknown to him at the time that he put forward the " 5-atom rule."14765381a, 1952, 1,