P. Lundgren
Sep 1, 1956
Citations
0
Influential Citations
2
Citations
Journal
Journal of Pharmacy and Pharmacology
Abstract
THE use of 2 : 4-diamino-5-phenylthiazole (amiphenazole, fenamizol, D.A.P.T.), as a morphine antagonist was reported by Shaw and Bentley in 1949l and 19522 and by Shaw and Shulman3 in 1955. Amiphenazole has also been used by Shulman et aL4 as a synergist with /?-methyl-/?ethylglutarimide (4-methyl-4-ethyl-2 : 6-dioxopiperidine, bemegride, NP 13) in the treatment of barbiturate intoxication. In the early part of 1955 amiphenazole was studied by Canback, and others, in this labor at or^^-^. During this work a rapid reliable method was required to investigate the stability of amiphenazole in pharmaceutical preparations. From an analytical point of view, published papers offer little about amiphenazole. From a paper by Davies et aL8, dealing with the synthesis and properties of 2 : 4-diaminothiazoles, it is known that amiphenazole is a monoacidic base [m.pt. of the picrate 189" to 191" C. (decomp.)]. Its soluble salts with halogen acids are white crystalline powders, stable to air. During the isolation of the free base, atmospheric oxidation readily produces tars. An aqueous solution of the hydrobromide or hydrochloride of amiphenazole with a slight excess of sodium hydrogen carbonate or ammonia solution deposits the base, which slowly becomes yellow and then brown. Amiphenazole is almost completely devoid of aromatic character ; it neither forms Schiff's bases with aldehydes nor undergoes diazotisation, and it does not give the carbylamine reaction.8 In aqueous solution the halogen salts of amiphenazole slowly undergo hydrolysis, to which the 4-amino-group is extremely sensitive. By refluxing a 5 per cent. aqueous solution of the amiphenazole hydrobromide for 3 hours Davies et aL8 prepared 2-amino-4-hydroxy-5-phenylthiazole. Finally, both amino-groups can be replaced by hydroxy-groups through acid hydrolysis (refluxing of the amiphenazole hydrochloride for 5 hours with diluted hydrochloric acid (I + 2) gave 2 : 4-dihydroxy-5-phenylthiazole8).