As part of a study of the chemistry and pharmacology of urethans, a number of substituted urethans have been prepared in this Laboratory, and it seemed desirable to record those that have not previously been described in the literature, and to describe improved or modified methods of preparation for some that have been reported already.These compounds have been prepared (1) by treating a solution of an amine in ether or benzene with the required amount of alkyl chlorocarbonate in the presence of an aqueous solution of sodium or potassium hydroxide, or (2) by heating together an amino compound and an alkyl chlorocarbonate with or without a solvent, or (3) by heating together a urethan with an acid chloride with or without a solvent.Preliminary observations on the pharmacological properties of some of these compounds are included in this paper but detailed studies will be reported elsewhere.
A group of more than sixty cyanine dyes and related compounds has been studiedla for chemotherapeutic activity against the naturally acquired Litomosoides carinii infestation in the wild cotton rat as part of a coordinated research program on filariasis under the auspices of thc Office of Scientific Research and Development. A similar study with a group of pyrryl, pyrimidyl and related cyanines was carried out simultaneously by Dr. A. D. Welch and his associate^^-^ at Western Reserve University.Care of the animals and administration of drugs was greatly facilitated by the use of special cages, holders, and feed cups designed by one of the authors (J. T. Litchfield, Jr.). The cages were made of a heavy wire mesh, were oblong in shape and of a size suitable for housing the rats individually. One end of the cage was designed as consisting of flanged sheet metal into which fitted a sliding door and to which either the holder or feed cup could be attached (FIGURE 1 ) . The holders were equipped with sliding doors at both ends and had a curved piece of metal extending most of the length inside the top, which was attached by springs to a metal bar outside the holder. With the holder in hand, slight pressure from the palm could be exerted on the bar, thus pressing the abdomen of the rat gently against the wire mesh bottom of the holder, through which intraperitoneal injections were then made. For drug diet administration, feed cups were attached to the metal flanges on the outside of the cages, thus allowing easy removal for daily filling and weighing. . Tests for chemotherapeutic activity were made in uivo against the adult filaria. Administration was usually by intraperitoneal injection every eight hours for eighteen doses with autopsy on the eighth day. The filaria were removed at autopsy, placed in a modified Sim's solution and examined for motility for 24 hours. The minimum curative dose was taken to be that dose of drug which killed 50 per cent or more of the adult filaria. Therapeutic indices were determined as the ratio of the maximum tolerated dose (M.T.D.) to the minimum curative dose (M.C.D.) based +This work was done under contract with the Office of Scientific Research and Development, the Office of the Surgeon General of the R. S. Army, the United States Public Health Service, and the University of Minnesota. Grateful appreciation is made to the Eastman Kodak Company and Parke, Davis and Company for supplying these compounds through the Chemotherapy Center.
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