Design and synthesis of novel inhibitors of HIV-1 reverse transcriptase.
Design and synthesis of novel inhibitors of HIV-1 reverse transcriptase.
复制标题
新型HIV-1逆转录酶抑制剂的设计与合成。
DOI：
10.1021/jm00012a014
复制
发表时间：
1995
影响因子：
7.3
通讯作者：
Johnson,F
中科院分区：
文献类型：
--
作者：
Maruenda,H;Johnson,F
RG-587,103；2-吡啶酮类化合物，如L 697,661,114(图1)。此外，突变和动力学研究提供了证据，证明HEPT、TIBO和奈韦拉平有共同的作用部位。12这被确定为调节位点RTiMS，当被这些分子中的任何一个占据时，RT的聚合酶活性被抑制。所有这些化合物都进行了广泛的构效关系研究。然而，似乎没有进行任何投资来开发HEPT系列的循环变体。阐述这类化合物似乎是一个吸引人的目标，因为可以获得关于这种分子的哪种构象形式与其生物活性有关的信息。这反过来将有助于开发这类类似物的特定子集。我们的第一个目标，也是本报告的主题，是开发一系列化合物，其中苯环相对于嘧啶环的旋转和定位受到限制。这一目标具有
RG-587, 10 3; and the 2-pyridinone derivatives, eg, L 697,661, 11 4 (Figure 1). Furthermore, mutational and kinetic studies have provided evidence that argues for a common site of action for HEPT, TIBO, and nevira-pine. 12 This has been identified as the modulatory site, RTiMS, and when occupied by any of these molecules the polymerase activity of RT is inhibited. 13’14 Extensive structure-activity studies have been con-ducted on all of these compounds. However, no inves-tigations seemed to have been made to develop cyclic variants in the HEPT series. Theelaboration of such compounds seemed to be an attractive objective because information might be obtained concerning which of the conformational forms of this molecule is associated with its biological activity. Thisin turn would aid in the development of a specific subset of analogs of this class. Our first goal, and the subject of this report, was the development of a series of compounds in which the rotation and positioning of the phenyl ring with respect to the pyrimidine ring is restricted. This objective had