Lead optimization of an acylhydrazone scaffold possessing antiviral activity against Lassa virus.
Lead optimization of an acylhydrazone scaffold possessing antiviral activity against Lassa virus.
复制标题
DOI：
10.1016/j.bmcl.2013.08.103
复制
发表时间：
2013-11-01
影响因子：
2.7
通讯作者：
Dai, Dongcheng
中科院分区：
文献类型：
--
作者：
Burgeson, James R.;Gharaibeh, Dima N.;Moore, Amy L.;Larson, Ryan A.;Amberg, Sean M.;Bolken, Tove' C.;Hruby, Dennis E.;Dai, Dongcheng
以前，我们报道了优化的抗病毒支架含有苯并咪唑和相关的杂环具有针对各种沙粒病毒的活性。这些系列化合物是通过400，000个小分子文库的HTS活动发现的，所述小分子文库使用与拉沙病毒包膜糖蛋白（LASV GP）结合的基于慢病毒的假型。该筛选还发现了基于酰腙支架的一系列替代的非常有效的沙粒病毒抑制剂。随后对该化学系列进行的SAR分析涉及整个化学框架的各种取代，沿着评估优选的立体化学。这些研究导致优化的类似物（ST-161）具有针对LASV的亚纳摩尔活性和针对沙粒病毒科中的许多其它病毒的亚微摩尔活性。
Previously we reported the optimization of antiviral scaffolds containing benzimidazole and related heterocycles possessing activity against a variety of arenaviruses. These series of compounds were discovered through an HTS campaign of a 400,000 small molecule library using lentivirus-based pseudotypes incorporated with the Lassa virus envelope glycoprotein (LASV GP). This screening also uncovered an alternate series of very potent arenavirus inhibitors based upon an acylhydrazone scaffold. Subsequent SAR analysis of this chemical series involved various substitutions throughout the chemical framework along with assessment of the preferred stereochemistry. These studies led to an optimized analog (ST-161) possessing subnanomolar activity against LASV and submicromolar activity against a number of other viruses in the Arenaviridae family.
登录
查看更多内容
影响因子：
3
作者：
Gong, Qingguo;Menon, Lakshmi;Ishima, Rieko
通讯作者：
Ishima, Rieko
影响因子：
3.5
作者：
Jordao, Alessandro K.;Sathler, Plinio C.;Cunha, Anna C.
通讯作者：
Cunha, Anna C.
影响因子：
7.3
作者：
Madsen, P;Ling, A;Lau, J
通讯作者：
Lau, J
影响因子：
7.3
作者：
Kuemmerle, Arthur E.;Schmitt, Martine;Barreiro, Eliezer J.
通讯作者：
Barreiro, Eliezer J.
影响因子：
7.3
作者：
Diaz, Philippe;Xu, Jijun;Naguib, Mohamed
通讯作者：
Naguib, Mohamed