1 Replacement of ester by amide in series of derivatives of diphenylacetic acid reduces the affinity for muscarine-sensitive. acetylcholine receptors of the guinea-pig ileum from 40-to 100-fold. With similar series of phenylacetic acid the reduction is only 2-to 4-fold. In both series changes in the comnposition of the onium group produce similar changes in the affinity of amides-and esters and it appears that the stiffness of the amide bond reduces the binding of the phenyl groups at the far end of the molecule from the onium atom. 2 Replacement of ester by amide in similar series of acetyl compounds reduces activity on the guinea-pig ileum over 1000-fold and on the frog rectus over 50-fold. Compounds with larger onium groups are antagonists on both preparations with log affinity constant around 3. The amides have similar affinity for electric eel acetylcholinesterase. 3 The amides are slightly bigger than the esters in solution and slightly more hydrophilic. 4 Replacement of ester by amide in acetylcholine reduces the proportion of gauche conformer about the C-C-bond from 100% to 39%. 5 The ability of acetylcholine to activate receptors is thought to depend on some degree of flexibility in the -CO-O-bond, though the hydration of the bond may also be important.

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Ultraviolet irradiation of papaverine N-oxide (2) in methanol gave papaverine (1) and 6,7-dimethoxy-2-(3',4'-dimethoxybenzyl)isocarbostyril (3). Irradiation of (2) in acetone resulted in the isolation of 7,8-dimethoxy-2-(3',4'-dimethoxybenzyl)-l,3-benz- oxazepine (4) by crystallization of the photolysate, and of 5,6-dimethoxy-2-(3',4'-di- methoxybenzy1)benzofuran-3-carboxaldehyde (6), 5,6-dimethoxybenzofuran-3-yl- 3',4'-dimethoxybenzyl ketone (7), 5,6-dimethoxy-2-(3',4'-dimethoxybenzyl)benzofuran (8), and papaverine by preparative thin-layer chromatography on silica gel. Evidence is presented in support of the formation of (6) and (7) from the valence tautomer (5) of the oxazepine (4), by acid-catalysed hydrolysis and rearrangement.

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