Althuis T H, Kadin S B, Czuba L J, Moore P F, Hess H J
J Med Chem. 1980 Mar;23(3):262-9. doi: 10.1021/jm00177a010.
A series of more than 50 new 3,4-dihydro-4-oxopyrimido[4,5-b]quinoline-2-carboxylic acid derivatives and related compounds with substituent variations at the 2, 3, and 5--9 positions was prepared and evaluated for antiallergy activity using the rat PCA assay. These compounds were obtained by the condensation of the appropriately substituted 2-aminoquinoline-3-carboxamides with dialkyl oxalates, followed by further chemical transformations. More than two-thirds of the compounds prepared exhibited intravenous activity ranging from 1 to 400 times disodium cromoglycate (DSCG). Structure--activity data suggest that the presence of a carboxylic acid moiety at the 2 position affords optimal potency and that esters are preferred for good oral absorption. Best oral activity, with ED50 values ranging from 0.3 to 3.0 mg/kg, was displayed by ethyl esters with methoxy and/or ethoxy groups at the 7 and 8 positions.
制备了一系列50多种新型的3,4-二氢-4-氧代嘧啶并[4,5-b]喹啉-2-羧酸衍生物以及在2、3和5-9位具有取代基变化的相关化合物，并使用大鼠PCA试验评估其抗过敏活性。这些化合物是通过适当取代的2-氨基喹啉-3-羧酰胺与草酸二烷基酯缩合，然后进行进一步的化学转化而获得的。所制备的化合物中超过三分之二表现出静脉活性，其活性范围是色甘酸二钠（DSCG）的1至400倍。构效关系数据表明，2位存在羧酸部分可提供最佳效力，而酯类对于良好的口服吸收是优选的。在7和8位带有甲氧基和/或乙氧基的乙酯表现出最佳的口服活性，ED50值范围为0.3至3.0 mg/kg。
