A straightforward synthesis of pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones was developed starting from 2-chloropyridine-3-carboxylic acid by esterification, nucleophilic aromatic substitution and amide formation in one step, and ring closure allowing their synthesis with two identical or two different group attached to nitrogen. The structural diversity of these [2,3-d]pyrimidine-2,4(1H,3H)-diones resulted in significant variation in the biopharmaceutical properties. This was reflected by the broad range in fasted state simulated intestinal fluid solubility values (12.6 μM to 13.8 mM), Caco-2 permeability coefficients (1.2 × 10⁻⁶ cm/s to 90.7 × 10⁻⁶ cm/s) and in vitro-predicted human in vivo intrinsic clearance values (0 to 159 ml/min/kg).

从2-氯吡啶-3-羧酸通过酯化，亲核芳族取代和酰胺形成一步开发了吡啶并[2,3 - d ]嘧啶-2,4（1 H，3 H）-二酮的简单合成方法，和闭环使它们的合成具有两个相同或两个不同的氮基团。这些[2,3 - d ]嘧啶-2,4（1 H，3 H）-二酮的结构多样性导致生物制药性能的显着变化。在禁食状态下模拟肠液的溶解度值范围很广（12.6μM至13.8 mM），Caco-2渗透系数（1.2×10 ^-6  cm / s至90.7×10 ）反映了这一点。^-6  cm / s）和体外预测的人体内固有清除率值（0至159 ml / min / kg）。