title: Synthesis and antifilarial activity of N-[4-[[4-alkoxy-3-[(dialkylamino)methyl]phenyl]amino]- 2-pyrimidinyl]-N'-phenylguanidines.
abstract: A series of N-[4-[[4-alkoxy-3-[(dialkylamino)methyl]phenyl]amino]- 2-pyrimidinyl]-N'-phenylguanidines have been synthesized for antifilarial evaluation. Reaction of the appropriate benzenamines with N-cyanoguanidine, followed by condensation of the resultant N-phenylimidodicarbonimidic diamides (V) with ethyl 4,4,4-trifluoro-3-oxobutanoate provided the intermediate N-(4-hydroxy-2-pyrimidinyl)-N'-phenylguanidines VIa. Alternatively, compounds VIa were synthesized by reaction of the requisite beta-keto esters (VII) with N-cyanoguanidine to give the (4-hydroxy-2-pyrimidinyl)cyanamides (VIII), followed by treatment with the desired benzenamines. Chlorination with POCl3 and condensation with the appropriate benzenamines (IX) generated the desired guanidines (X). Antifilarial activity was confined to adult Litomosoides carinii infections, and a structure-activity relationship for this activity is discussed. Lack of activity against L. carinii microfilaria and adult Brugia pahangi infections preclude further work in this area pending evaluation in additional experimental models.
mesh_terms: D000818:Animals; D000969:Antinematodal Agents; D002009:Brugia / Q000187:drug effects; D005370:Filarioidea / Q000187:drug effects*; D005849:Gerbillinae; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology; D008842:Microfilariae / Q000187:drug effects
chemical_list: D000969:Antinematodal Agents; D006146:Guanidines