Elslager E F, Hess C, Johnson J, Ortwine D, Chu V, Werbel L M
J Med Chem. 1981 Feb;24(2):127-40. doi: 10.1021/jm00134a002.
A series of N2(and N4)-aryl-N4(and N2)-[(dialkylamino)alkyl]-2,4-quinazolinediamines has been synthesized for antimalarial evaluation. Condensation of the appropriate 2,4-dichloroquinazoline (IV) with the requisite N,N-dialkylalkylenediamine afforded a series of 2-chloro-N-[(dialkylamino)alkyl]-4-quinazolinamines (V) which were condensed with the appropriate arylamine to provide the corresponding N2-aryl-N4-[(dialkylamino)alkyl]-2,4-quinazolinediamines (VI). Hydrolysis of 2,4-dichloroquinazoline to 2-chloro-4-quinazolinol was followed by condensation with the appropriate N,N-dialkylalkylenediamine to give an array of 2-[[(dialkylamino)alkyl]amino]-4-quinazolinols (IXa). Chlorination with phosphorus oxychloride and condensation with a requisite arylamine provided the N2-[(dialkylamino)alkyl]-N4-phenyl-2,4-quinazolinediamines (X). Antimalarial activity was general among the N2-aryl-N4-[(dialkylamino)alkyl]-2,4-quinazolinediamines (VI), while the reverse isomers were of lower activity. Phototoxic liability precluded clinical evaluation of a member of the series.
已合成了一系列N2（和N4）-芳基-N4（和N2）-[(二烷基氨基)烷基]-2,4-喹唑啉二胺用于抗疟评估。合适的2,4-二氯喹唑啉（IV）与所需的N,N-二烷基亚烷基二胺缩合得到一系列2-氯-N-[(二烷基氨基)烷基]-4-喹唑啉胺（V），其再与合适的芳胺缩合以提供相应的N2-芳基-N4-[(二烷基氨基)烷基]-2,4-喹唑啉二胺（VI）。2,4-二氯喹唑啉水解为2-氯-4-喹唑啉醇，随后与合适的N,N-二烷基亚烷基二胺缩合得到一系列2-[[(二烷基氨基)烷基]氨基]-4-喹唑啉醇（IXa）。用三氯氧磷氯化并与所需的芳胺缩合得到N2-[(二烷基氨基)烷基]-N4-苯基-2,4-喹唑啉二胺（X）。N2-芳基-N4-[(二烷基氨基)烷基]-2,4-喹唑啉二胺（VI）普遍具有抗疟活性，而其反式异构体活性较低。光毒性使得该系列中的一个成员无法进行临床评估。
