A series of aw-di-(p-aminophen0xy)alkanes of the general formula (I; R = R' = H) has been prepared and tested against Schistosoma mansoni infections in mice. Modifications of this fundamental molecular type which have been explored, in an attempt to establish a structure-activity relationship, include substitution in the amino-groups, the rings, and the central chain, and replacement of the central chain by other linkages. Many of the compounds exhibit high schistosomicidal activity.SCHISTOSOMIASIS is one of the greatest unsolved problems in tropical medicine, and an inexpensive and safe drug which can be administered orally is an outstanding need. An extensive programme of work has been pursued in these laboratories during the last few years in the search for such a drug and several hundred compounds have been synthesised, and screened by our biological colleagues against Schistosoma mansoni.Schistosomicidal activity was discovered early in 1952 in a series of aromatic diaminesThe Chemotherajby of Schistosomiasis. Part I .
3299of the general formula (I ; R = R' = H ; n = 3-9) , many of which had been prepared some ten years earlier for another purpose.A preliminary announcement 1 of this work was made after the disclosure in the patent literature that the same series had been investigated independently by Raison and Standen.2 Full details of the biological tests and the results obtained are being recorded elsewhere.3 In this paper, the first of a series dealing mainly with compounds containing the $-aminophenoxyalkyl group, we shall describe the preparation of some primary, secondary, and tertiary amines of type (I) together with derivatives and analogues in which, for example, the central chain has been modified or further substituents introduced into the rings. Most of the simpler compounds have already been mentioned in patent specifications.415 Since they were generally obtained by conventional methods, in reasonable yields, and with satisfactory analyses, and their melting points are recorded in these patents, further preparative details, solvents for recrystallisation, analytical figures, etc. , have in most cases been omitted from this paper.The di(nitrophen0xy)alkanes were obtained by condensation of potassium nitrophenoxide with the appropriate dibromide. Compounds not previously reported are listed in Table 1. Reduction of the dinitro-compounds to the diamines ( Table 2) was effected either catalytically or by sodium sulphide. An alternative route also employed in some instances was the condensation of the appropriate acetamidophenol with the dibromide, followed by hydrolysis of the acetyl groups. The unsymmetrical dinitrocompounds were prepared by reaction of 1 : 5-dibromopentane with a limited amount of potassium 9-nitrophenoxide to give 5-P-nitrophenoxypentyl bromide, followed by further reaction with potassium o-or m-nitrophenoxide.At one time a substantial amount of 1 : 8-dibromo-octane was needed and its preparation from the readily available 1 : 4-dibromobutane was undertaken. Of the methods des...
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