Derivatives of 4-(2-N,N-Di-n-propylaminoethyl)-5-hydroxyindole: Synthesis and Pharmacological Effects
Abstract5-Methoxy-l-methyl-4-(2-N,N-di-n-propylaminoethyl)indole (12) was synthesized from 5-hydroxyindole by a multistep synthesis. This target compound was designed as a bioisostere of “p-dimethoxy” catechol congeners of dopaminergic agonists derived from a variety of ring systems, in some of which p-dimethoxy-substituted systems are potent, active dopaminergic agonists. To complete the indole series, all possible combinations of N- and O-demethylated derivatives of 12 were prepared and were also evaluated pharmacologically. All members of this indole-derived series showed a low order of cardiovascular activity, which appeared to be independent of dopamine receptors. The lack of dopaminergic activity of 12 is cited as yet another example of the unpredictable effect of replacement of the catechol moiety of a dopaminergic agonist with a p-dimethoxy moiety.
p-Dimethoxy-substituted trans-octahydrobenzo[f]- and -[g]quinolines: synthesis and assessment of dopaminergic agonist effects.
The N-n-propyl homologues of the title compounds were prepared for further assessment of the ability of the "p-dimethoxy" moiety to confer dopaminergic agonism upon a variety of ring systems. Both the angularly and the linearly annulated trans-benzoquinoline ring derivatives displayed prominent DA2 dopaminergic effects on the peripheral sympathetic nerve terminal and displayed postjunctional dopamine receptor agonist properties in the striatum. It is speculated that the angular octahydrobenzo[f]quinoline derivative (but not the linear octahydrobenzo[g]quinoline derivative) may owe its dopamine-like effects to metabolic activation phenomena. In contrast, the cis-fused isomer of the angularly annulated benzoquinoline was inactive, as was the simple benzene derivative N,N-di-n-propyl-beta-(2,6-dimethoxyphenyl)ethylamine.
Intensification of Bubble Disintegration and Dispersion by Mechanical Stirring in Gas Injection Refining
Water model experiments were performed for establishing highly efficient gas injection refining processes. Mechanical stirring was applied to disintegrate the injected bubbles and to disperse them widely in the bath. The bubble disintegration and dispersion were investigated by changing rotation mode (direction of rotation), rotation speed, blade size of the impeller and gas flow rate. Forward rotation of the impeller induced a stable tangential flow and could not disperse bubbles in the bath due to formation of a vortex around the impeller shaft. The tangential flow could be suppressed by forward–interrupt rotation, which could reduce the vortex formation to some degree. However, forward–interrupt rotation could not disperse the bubbles widely in the bath. Forward–reverse rotation could prevent the vortex formation completely and create a strong shear stress field, which intensified the bubble disintegration and dispersion in the bath. Higher impeller rotation speed and larger blade length in forward–reverse rotation could enhance the bubble disintegration and make the dispersed bubbles smaller. The bubble dispersion zone became wider with larger blade length. The bubble size tended to be larger at higher gas flow rates. However, its dependence on the gas flow rate became smaller at higher impeller rotation speed.