A small library containing 3-hydroxyquinazoline-2,4(1H,3H)-dione and 1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one scaffolds was obtained via the copper(I)-catalyzed azidealkyne cycloaddition (CuAAC) reaction and evaluated for their anti-HIV activity in MT-4 cells. Among the synthesized compounds, several 1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-one derivatives showed remarkable anti-HIV potency with EC₅₀ values ranging from 0.92 to 26.85 µM. The most active one, IIA-2, also showed remarkable and selective potency against HIV type 1 integrase (IN). To the best of our knowledge, this is the first report showing that 1-hydroxypyrido[2,3-d]pyrimidin-2(1H)-ones are selective HIV IN inhibitors. Preliminary structure-activity relationship (SAR) studies suggested that the divalent metal ion chelators and the nature and position of substituents around the core are important for antiviral potency. Molecular modeling has been used to predict the binding site of the pyrido[2,3-d]pyrimidin-2(1H)-one core in HIV type 1 IN and suggestions are made for improvement of its inhibitory activity.

通过铜（I）-获得了一个小型文库，该文库包含3-羟基喹唑啉-2,4（1 H，3 H）-二酮和1-羟基吡啶并[2,3 - d ]嘧啶-2（1 H）-one支架。催化叠氮炔环加成反应（CuAAC），并评估其在MT-4细胞中的抗HIV活性。在合成的化合物中，几种1-羟基吡啶并[2,3- d ]嘧啶-2（1 H）-one衍生物显示出显着的抗HIV效力，EC ₅₀值为0.92至26.85 µM。最活跃的IIA-2，也显示出对HIV 1型整合酶（IN）的显着选择性作用。据我们所知，这是第一份报告显示1-羟基吡啶并[2,3 - d ]嘧啶-2（1 H）-是选择性的HIV IN抑制剂。初步的结构-活性关系（SAR）研究表明，二价金属离子螯合剂以及核心周围取代基的性质和位置对于抗病毒效力很重要。分子模型已被用来预测1型HIV感染中的吡啶并[2,3- d ]嘧啶2（1 H）-一个核心的结合位点，并提出了改善其抑制活性的建议。