THE SCHISTOSOMICIDAL AND TOXIC EFFECTS OF SOME N‐p‐AMINOPHENOXYALKYLAMIDES

Abstract

Several N-(co-p-aminophenoxyalkyl)amides were active against Schistosoma mansoni in mice.One of the most effective, N-(5-p-aminophenoxypentyl)benzamide (M&B3002), acted more rapidly than lucanthone on adult worms but less rapidly than antimony potassium tartrate. It was inactive against immature worms. This compound and M&B2948A (N-(5-p-aminophenoxypentyl)phthalimide) were both active against S. mansoni in hamsters. In monkeys M&B2948A was inactive, whilst M&B3002 was not tested for therapeutic activity. Several of the compounds were examined for the production of visual impairment in cats. Although this property was not entirely absent, its incidence was very much lower in this amide series than among other co-paminophenoxyalkyl derivatives not containing an amide group. M&B3002 and M&B2948A produced impairment of vision in only a small proportion of the large number of cats tested. The general toxicology of the two drugs was studied in several species, and also their absorption and excretion in mice and rats; this was to provide information for a clinical trial.

Effects of Internally Administered N-[5-( 4-Aminophenoxy)Pentyl]Phthalimide on Wool Follicles and Skin of Sheep

“…However, it has been found to cause blindness in sheep when administered at dose rates greater than 700 mg/kg (D. A. Tunks, personal communication), although retinotoxic effects had previously only been reported in cats (Collins et al 1959). Consequently, other compounds are being examined in the search for a depilating agent without retinotoxicity (Rigby et al 1980).…”

The Antischistosomal and Retinotoxic Effects of Some Nuclear Substituted Aminophenoxyalkanes

“…The activity of M&B 2948A(I) against Schistosoma inansoni in mice was reported by Collins, Davis, Edge, Hill, Reading & Turnbull (1959), who also found that it produced ocular effects in only a small proportion of the cats tested, in contrast to 1,5-di-(p-aminophenoxy)pentane and its homologues, which with the exception of the co NH> O(CH2)I Ns I 3 NH 0 OR 2 2. 5 'co NH )2 \32/ (I) (II) NH2K< O (CH2 ) 7CH3 NH 2 2 (7 3 dodecane were all retinotoxic (Collins, Davis, Edge & Hill, 1958).…”

“…Effect of N-substitution (Table 9) The results given here demonstrate that N-substituted compounds were active although they were sometimes less so than the corresponding primary amines, as found by Raison & Standen (1955); Gorvin, Raison, Solomon, Standen & Walls (1957) and Collins et al (1958Collins et al ( , 1959.…”

“…Nuclear substitution in J-p-aminophenoxy-S-phthalimidopentane (Table 8) 2-Methoxy substitution to give M&B 3530 had little effect on the activity or toxicity of the parent compound (M&B 2948A, I) (Collins et al, 1959), and since M&B 3530 was rather less accessible chemically and unlikely to be more active in man, it was not considered for clinical trial. The most interesting compound in the group, M&B 6354, was retinotoxic in 6/12 cats at a daily dose of 0.4 g/kg given over 6-12 days, and consequently was not considered for clinical trial.…”

“…The activity of M&B 2948A(I) against Schistosoma inansoni in mice was reported by Collins, Davis, Edge, Hill, Reading & Turnbull (1959), who also found that it produced ocular effects in only a small proportion of the cats tested, in contrast to 1,5-di-(p-aminophenoxy) Edge & Hill, 1958). An account of its first trial against S. haematobium in African schoolchildren is given by Alves, Harper & Hill (1961).…”