Synthesis and biological activity of conformationally restricted indole-based inhibitors of neurotropic alphavirus replication: Generation of a three-dimensional pharmacophore.
Synthesis and biological activity of conformationally restricted indole-based inhibitors of neurotropic alphavirus replication: Generation of a three-dimensional pharmacophore.
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DOI：
10.1016/j.bmcl.2021.128171
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发表时间：
2021-08-15
影响因子：
2.7
通讯作者：
Larsen SD
中科院分区：
文献类型：
--
作者：
Barraza SJ;Sindac JA;Dobry CJ;Delekta PC;Lee PH;Miller DJ;Larsen SD
我们以前曾报道过吲哚为基础的CNS活性抗病毒药物治疗嗜神经性甲病毒感染的发展，但进一步优化是由于缺乏知识的分子靶点和结合位点。在这里，我们描述了一系列的构象限制的类似物的设计，合成和评价的双重目标，提高效力/选择性和确定最具生物活性的构象。虽然这一运动只是适度成功地提高效力，明确定义的SAR的刚性类似物，使三维药效团的定义，我们相信这将是有价值的，在进一步的类似物设计和虚拟筛选替代抗病毒的线索。
We have previously reported the development of indole-based CNS-active antivirals for the treatment of neurotropic alphavirus infection, but further optimization is impeded by a lack of knowledge of the molecular target and binding site. Herein we describe the design, synthesis, and evaluation of a series of conformationally restricted analogues with the dual objectives of improving potency/selectivity and identifying the most bioactive conformation. Although this campaign was only modestly successful at improving potency, the sharply defined SAR of the rigid analogs enabled the definition of a three-dimensional pharmacophore, which we believe will be of value in further analog design and virtual screening for alternative antiviral leads.
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影响因子：
3.6
作者：
ALLINGER, NL;TUSHAUS, LA
通讯作者：
TUSHAUS, LA
影响因子：
7.6
作者：
Colombo, Gaia;Lorenzini, Luca;Scagliarini, Alessandra
通讯作者：
Scagliarini, Alessandra
影响因子：
--
作者：
Delekta PC;Raveh A;Larsen MJ;Schultz PJ;Tamayo-Castillo G;Sherman DH;Miller DJ
通讯作者：
Miller DJ
影响因子：
7.3
作者：
Kazuta, Y;Hirano, K;Shuto, S
通讯作者：
Shuto, S
影响因子：
6.4
作者：
Peng, Weiping;Peltier, Daniel C.;Miller, David J.
通讯作者：
Miller, David J.