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Credit: Ernest Forneau, 1872-1949 / [Thomas Anderson Henry]. Source: Wellcome Collection.
![Mont6zin, Bull. Soc. Chim. biol., 1944, 26, 516). This line of work was then extended to the examination of muscarine-like action in amino-acetals of the general types (I) and (II). All the examples examined showed this type of action, which reached a maximum in type (I) with R = H and R' = Me, and in type (II) with R = H, but fell off when R or R' was increased and disappeared when R = R' = Ph. It was also reduced by the insertion of a hydroxyl group (with Bovet, Mont6zin, J. P. Fourneau, and Mile. Chantalou, Ann. Pharm. Fran$, 1944, 2, 120; 1945, 3, 114). This was followed by a paper dealing with the complex reactions, simulating those of nicotine, muscarine, and curare, shown by a series of halogenated derivatives of alkyltrimethylammonium salts (with D. Bovet and F. Bovet, ibid., 1946, 4, 166). I{Me8N-CH2-CH-0-CRR,-0*CH2 I{Me,N-CH2-CH-OCHR-CH2 (i) i————J A—-J (ii) The work so far mentioned relates almost wholly to symptomatic drugs, but Fourneau also made notable contributions to chemotherapy proper. In the early years of this century great interest was aroused by Thomas’s successful treatment of trypanosomiasis in animals with atoxyl (Proc. Roy. Soc., 1905, B, 76, 589) which was shown by Ehrlich and Bertheim to be sodium hydrogen ^-aminophenylarsonate, ^>-NH2*C6H4*AsO(OH)*ONa (Ber., 1907, 40, 3292), and they in common with Fourneau (J. Pharm. Chim., 1907, [vi], 25, 332, 528) agreed that it was first made by B6champ in 1863. This inaugurated a period of great activity, during which the important drug “ Salvarsan ” was discovered in Germany, and Ehrlich and Hata published their conclusions on the therapeutic superiority of organic arsenical compounds containing arsenic in the tervalent form over the phenylarsonic acid series in which arsenic is quinque- valent (Die experimentelle Chemotherapie der Spirillosen, Berlin, 1911). Fourneau gave reasons for disagreement with these views and promised further work on the subject [Ann. Inst. Pasteur, 1921, 35, 571). The results were published in two remarkable papers {ibid., 1923, 37, 551; 1926, 40, 933) in which he had as colleagues M. Navarro-Martin, M. and Mme. Tr6fouel, and Mme. de Lestrange-Tr6vise. The preparation of a large number of arsenical compounds, many of them already known, was described and there was recorded for each the maximum tolerated dose and the effective curative dose in animals infected with trypanosomes or spirochaetes. The effects, on efficiency against each type of infection, of the nature and orientation of each substituent alone or in conjunction were discussed in detail. Among the points stressed by Ehrlich and Hata against quinquevalent arsenic compounds was their liability to cause nervous disorders including ocular trouble, and Fourneau was at pains to point out that as a number of his compounds did not produce these effects in the experimental animals this kind of action could not be attributed to the arsonic acid group. Among the compounds dealt with were the ten isomeric aminohydroxyphenylarsonic acids, which were fully described later, with a comparison of their pharmacological constants (with M. and Mme. Tr6fouel and Mile. Benoit, Bull. Soc. chim., 1927, [iv], 41, 499), and one of these in the form of its IV-acetyl derivative, viz., 3-acetamido-4-hydroxyphenylarsonic acid, is the well-known drug “ Stovarsol ” which was adopted in the British Pharmacopoeia in 1936 under the name acetarsol. The drug now seems to be used principally for the treatment of amoebiasis and Trichomonas vaginalis and for congenital syphilis in young children because it can be administered orally. It should be noted that 3-amino-4-hydroxyphenylarsonic acid had already been made by Ehrlich and Bertheim {Ber., 1912, 45, 756) during their preparation of “ Salvarsan,” but its recognition as the basis of a useful drug was undoubtedly the result of the careful work of Fourneau and his colleagues on its preparation and pharmacological action. The series also included “ Orsanine,” 4-acetamido-2-hydroxyphenylarsonic acid, which was rather more toxic than “ Stovarsol ” and unlike the latter is an effective trypanocide (cf. Walls, Chem. and Ind., 1951, 607). Among other arsenic compounds prepared by Fourneau may be mentioned the optically active forms of methyltryparsamide (A-p-arsonophenyl-p-methylglycine amide, NH2-C0-CHMe-NH-C6H4-As03H2), obtained by the use of quinine, which were used for the resolution of synthetic (d;)-ephedrine (with Nicolitch, Bull. Soc. chim., 1928, [iv], 43, 1232). Special interest also attaches to the series of diarsonic acid derivatives of various aryl nuclei, which exhibited a reversal of the trypanocidal action of the monoarsonic acids, being active against T. congolense but inactive towards T. brucei (with M. and Mme. Tr6fouel, Bovet, and Koetschet, Compt. rend., 1933, 196, 1173) and to the so-called “ alcoholic arsonic acids,” such as 4-amino-3-hydroxymethylphenylarsonic acid, NH2*C6H3(CH2*0H),As03H2, which in](https://iiif.wellcomecollection.org/image/b30633588_0006.jp2/full/800%2C/0/default.jpg)
