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The levels of antidopaminergic and anticholinergic activities of neuroleptics, 4-piperazinyl-10H-thienobenzodiazepines, are modulated by imposing steric impedence to the piperazine ring. The optimum situation in favor of the anticholinergic action is reached in compound 5, 2,3-dimethyl-7-fluoro-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine, where a maximum activity (equivalent to hyoscine), as measured by the [3H]QNB receptor binding assay, is obtained. The structure-activity relationships found highlight the importance of certain spatial dispositions of the distal piperazine nitrogen (electron lone pair) with respect to the tricyclic system. The evidence for molecular topography of these compounds is presented from X-ray, NMR, and other physical data. The conformational aspects for correspondence to the relevant receptors are discussed.

The steric effects of substituents and the position of protonation in strongly acidic media are discussed in terms of the changes observed in ultraviolet and n m r . absorption. A new series of 1 -pentafluorophenylpyrazoles has been synthesrsed, and their spectra are compared with those of the parent pyrazoles. Twenty-five commonly occurring bands in the infrared spectra of 1 -phenylpyrazoles are tabulated and assignments have been made.FURTHER to recent ultraviolet ( U . V . ) ~~ and nuclear magnetic resonance (n.m.r,)5-7 spectroscopic studies, we report an investigation of seventy 1-phenylpyrazole (I) derivatives by u.v., n.m.r., and infrared (ix.) methods.