The title compound, 5, was prepared and found to be a potent diuretic in the rat. At 27 mg/kg, urine output was 250% of the saline control, and the excretion of electrolytes was similar to th^hydrochlorothiazide control. At 80 mg/kg, the potassium excretion was the same as the saline control, and the sodium and chloride excretions more than doubled. Several analogues were prepared and tested. Some show diuretic activity.
A straighforward synthesis of Z,Z,Z-5,8,11-eicosatrienoic acid is described that gives a pure product without chromatography. The C2o-polyacetylenic acid is purified by recrystallization and then reduced by a Lindlar catalyst in an aprotic solvent with a trace quantity of quinoline.Lipids 18:894-895, 1983.
A mercapto analogue of histidine (1), (RS)-2-mercapto-3-(5-imidazolyl)propionic acid (2), was prepared by treatment of (RS)-2-bromo-3-(5-imidazolyl)propionic acid with trithiocarbonate. Decomposition of the resulting intermediate with hydrochloric acid followed by Sephadex G-15 chromatography permitted isolation of 2 as a hydrobromide complex having unusual stability and properties as evidenced by IR and 1H NMR data. The potency of this complex in inhibiting tissue (Rana catesbiana) collagenase was estimated by radial diffusion assay. The amount of 2 required to produce 50% inhibition was 3.8 +/- 1.5 mM compared to 8.7 +/- 2.5 mM for cysteine. Preliminary tests of oxygen susceptibility, mutagenicity, and toxicity suggest that this substance may warrant study as a therapeutic agent for control of collagenase-linked corneal ulcerations.
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