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The preparation, isolation, and melting points of 45 new 4-alkoxy-A,A-dialkyl-l-naphthamidine hydrochlorides with the alkoxy alkyl = Me through C13H» and the A-alkyl = Et through C8Hl7 are outlined. A brief discussion of the limitations of several synthetic routes to sterically hindered amidines is given. Approximate oral LD» values and therapeutic indices (TI) against the cestodes (tapeworms) Hymenolepis nana and Oochoristica symmetrica of these and related -naphthamidines in the mouse are given. A broad band of effective compounds is found at the sum of the number of carbons on O (Cor) plus twice the number of carbons on each (of two identical) alkyl groups on one N (2Cnr) = 12-ca. 23. A narrow band of maximum TI exists at Cor + Cnr = 10-13. Branching at the N (comparison of A,A-di-i-Pr with A)A-di-Et) does not effect the TI. Presence of hydrophilic groups or benzene rings on an amidine N destroyed activity, in the few cases studied. H. nana was much more readily eliminated than 0. symmetrica from the mouse.However results with neither of these adequately matched the structure-activity relationships found in the cestodes of dog and cats: Taenia pisiformis, Dipylidium caninum, Hydatigera taeniaformis, or Spirometra mansonoides. Individual amidines were effective against each of these, but the best compounds against all 4 species in the dog and cat are grouped at Cor ^4 and Cnr ^4. Bunamidine (4-hexyloxy-A,A-dibutyl-l-naphthamidine) has been found to be a "broad spectrum" cestocide effective against a variety of cestodes of veterinary significance in farm animals, and to be effective against adult Echinococcus spp. in dogs. These cestodes, in the larval form, are significant pathogens of man as well as farm animals.* To whom correspondence should be addressed.(1) (a) Department of Organic Chemistry, (b) Department of Experimental Therapeutics.(2) M. Harfenist, J. Med. Chem., 6, 361 (1963).

Die Alkoxynaphthonitrile (I) lassen sich durch Erhitzen mit den aus den entsprechenden sekundären Aminen (IV) und Äthylmagnesiumbromid darstellbaren Dialkylaminomagnesiumbromiden (II) zu den Amidinen (III) umsetzen.