Angelo M M, Ortwine D, Worth D F, Werbel L M
J Med Chem. 1983 Sep;26(9):1311-6. doi: 10.1021/jm00363a017.
A series of N2-1H-benzimidazol-2-yl-N4-phenyl-2,4-pyrimidinediamines and N2-1H-benzimidazol-2-yl-5,6,7,8-tetrahydro-N4-phenyl-2,4-quinazolinediamines (XI) was synthesized for antifilarial evaluation. Condensation of the requisite beta-keto ester (VI) with N-cyanoguanidine afforded 2-pyrimidinylcyanamides (VIIa,b) and (5,6,7,8-tetrahydro-4-hydroxy-2-quinazolinyl)cyanamide (VIIc). Reaction of VII with a substituted o-phenylenediamine gave 2-(1H-benzimidazol-2-ylamino)-4-pyrimidinols and 2-[(5,6-dichloro-1H-benzimidazol-2-yl)amino]-5,6,7, 8-tetrahydro-4-quinazolinol (IX). Chlorination with phosphoryl chloride, followed by condensation with the appropriate substituted benzenamine, gave the desired N2-1H-benzimidazol-2-yl-N4-phenyl-2,4-pyrimidinediamines and N2-1H-benzimidazol-2-yl-5,6,7,8-tetrahydro-N4-phenyl-2,4-quinazolinediamines (XI). None of these compounds possessed antifilarial activity against Litomosoides carinii or Brugia pahangi infections in jirds.
合成了一系列N2 - 1H - 苯并咪唑 - 2 - 基 - N4 - 苯基 - 2,4 - 嘧啶二胺和N2 - 1H - 苯并咪唑 - 2 - 基 - 5,6,7,8 - 四氢 - N4 - 苯基 - 2,4 - 喹唑啉二胺（XI）用于抗丝虫活性评价。将所需的β - 酮酯（VI）与N - 氰基胍缩合得到2 - 嘧啶基氰胺（VIIa,b）和（5,6,7,8 - 四氢 - 4 - 羟基 - 2 - 喹唑啉基）氰胺（VIIc）。VII与取代的邻苯二胺反应得到2 - （1H - 苯并咪唑 - 2 - 基氨基） - 4 - 嘧啶醇和2 - [（5,6 - 二氯 - 1H - 苯并咪唑 - 2 - 基）氨基] - 5,6,7,8 - 四氢 - 4 - 喹唑啉醇（IX）。用磷酰氯氯化，然后与适当的取代苯胺缩合，得到所需的N2 - 1H - 苯并咪唑 - 2 - 基 - N4 - 苯基 - 2,4 - 嘧啶二胺和N2 - 1H - 苯并咪唑 - 2 - 基 - 5,6,7,8 - 四氢 - N4 - 苯基 - 2,4 - 喹唑啉二胺（XI）。这些化合物对沙土鼠体内的卡里尼丝虫或马来布鲁线虫感染均无抗丝虫活性。
