The 3-and 4benzoylpiperidines and 3-benzoylpyrrolidines were prepared by the reaction of l-acetylisonipecotoyl or 1-acetylnipecotoyl chloride with a substituted aromatic compound under Friedel-Crafts conditions or by treatment of the cyanopiperidines and pyrrolidines with an arylmagnesium halide. Alkylation gave the I-substituted compounds which were evaluated as CNS depressants. The I-substituted 4(p-fluorobenzoyl)piperidines were the most active compounds, several of which were more potent than chlorpromazine, triperidol, or haloperidol in the fighting mouse assay.

No abstract

Human serum, human transferrin (TF), and the iron chelator 1,10-phenanthroline (OP) produce iron-reversible fungistatic activity which has been attributed to simple iron deprivation. In this study, the influence of the size of the inoculum on the inhibitory activity of serum, TF, and OP prepared with the same iron-binding capacity (2.5 ,ug/ml) for Rhizopus oryzae and Trichophyton mentagrophytes was examined. Inhibition was monitored in liquid microcultures maintained at 37°C and pH 7.4 to 7.5 by measuring the change in absorbance density. Increasing the number of spores in the inoculum disrupted the fungistatic activity of serum and TF, but not that of OP. The dilution at which OP lost fungistatic activity was not affected by the number of spores in the inoculum and was the same for both fungi. The dilution at which TF and serum lost fungistatic activity was dependent upon both the quantity of the inoculum and the species offungus. The number of viable spores, rather than the total number of spores in the inoculum, was determined to be important in overcoming the inhibition of fungal growth by serum and TF. The fungistatic activity of serum and TF could be diminished by the preexposure of the serum to viable but nongrowing spores. Direct and indirect fluorescence studies indicated that both T. mentagrophytes and R. oryzae absorbed TF. Glucose uptake by R. oryzae was inhibited by a 4-h exposure to 5.0 to 0.15 mg of apotransferrin per ml. These results suggest that the fungistatic activity of TF for R. oryzae and T. mentagrophytes may not be attributable to simple iron deprivation and raise the possibility of a requirement for a direct interaction. Human serum in vitro has fungistatic properties which have been attributed to the ironbinding glycoprotein transferrin (TF) (7, 10, 12, 21, 22). Two lines of direct evidence have implicated TF in this activity. First, purified TF added to medium has been demonstrated to inhibit fungal gro(wth (12, 20, 21). Second, the removal of TF from serum by affinity chromatography abolished the fungistatic activity of serum (12). The mechanism by which TF inhibits fungal growth is thought to be related to the capacity of the protein to tightly bind and thus reduce the presence of available iron to a level below that required to support fungal growth (22). The previously observed disruption of antifungal activity by the addition of iron-containing compounds to either serum-or TF-containing media is consistent with this explanation of the mechanism (7, 10, 12, 20, 21).

Indolo[1,2‐c] quinazolines, indolo[1,2‐d] [1,4]benzodiazepines, indolo [1,2‐d] [1,4]benzodi‐azepin‐6‐ones and benzimidazo[1,2‐d] [1,4] benzodiazepin‐6‐ones were synthesized. In an acid medium, the indoloquinazolines were produced from 2‐(o‐aminophenyl)indole and acyl halides. However, in the presence of sodium acetate, the acylated amine was obtained and was cyclized to the indolobenzodiazepinones using sodium hydride. The syntheses are described in detail and characterization data are given.

2‐Amino‐3‐benzoylphenylacetic acid, sodium salt was prepared from indoline through a process applicable to large scale production.