2'-(4-(2-(4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)phenyl)benzo[d]thiazole-6-carboxamido)phenyl)-6-methyl-[2,6'-bibenzo[d]thiazole]-7-sulfonic acid | 1363454-28-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2'-(4-(2-(4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)phenyl)benzo[d]thiazole-6-carboxamido)phenyl)-6-methyl-[2,6'-bibenzo[d]thiazole]-7-sulfonic acid
• 英文别名: Ksc-16-186_mdf029150；2-[2-[4-[[2-[4-(9H-fluoren-9-ylmethoxycarbonylamino)phenyl]-1,3-benzothiazole-6-carbonyl]amino]phenyl]-1,3-benzothiazol-6-yl]-6-methyl-1,3-benzothiazole-7-sulfonic acid
• CAS: 1363454-28-7
• 化学式: C₅₀H₃₃N₅O₆S₄
• 分子量: 928.106
• InChiKey: MWGRINMDCSHCFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.9
• 重原子数：
  65
• 可旋转键数：
  10
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  254
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2'-(4-(2-(4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)phenyl)benzo[d]thiazole-6-carboxamido)phenyl)-6-methyl-[2,6'-bibenzo[d]thiazole]-7-sulfonic acid 在 吗啉 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以1.5 mg的产率得到2'-(4-(2-(4-aminophenyl)benzo[d]thiazole-6-carboxamido)phenyl)-6-methyl-[2,6'-bibenzo[d]thiazole]-7-sulfonic acid
  参考文献：
  名称：

  Optimization of Potent Hepatitis C Virus NS3 Helicase Inhibitors Isolated from the Yellow Dyes Thioflavine S and Primuline

  摘要：

  A screen for hepatitis C virus (HCV) NS3 helicase inhibitors revealed that the commercial dye thioflavine S was the most potent inhibitor of NS3-catalyzed DNA and RNA unwinding in the 827-compound National Cancer Institute Mechanistic Set. Thioflavine S and the related dye primuline were separated here into their pure components, all of which were oligomers of substituted benzothiazoles. The most potent compound (P4), a benzothiazole tetramer, inhibited unwinding >50% at 2 +/- 1 mu M, inhibited the subgenomic HCV replicon at 10 mu M, and was not toxic at 100 mu M. Because P4 also interacted with DNA, more specific analogues were synthesized from the abundant dimeric component of primuline. Some of the 32 analogues prepared retained ability to inhibit HCV helicase but did not appear to interact with DNA. The most potent of these specific helicase inhibitors (compound 17) was active against the replicon and inhibited the helicase more than 50% at 2.6 +/- 1 mu M.

  DOI：

  10.1021/jm300021v
• 作为产物：
  描述：

  FMOC-4-氨基苯甲酸 在 吡啶 、 氯化亚砜 作用下， 反应 36.0h， 生成 2'-(4-(2-(4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)phenyl)benzo[d]thiazole-6-carboxamido)phenyl)-6-methyl-[2,6'-bibenzo[d]thiazole]-7-sulfonic acid
  参考文献：
  名称：

  Optimization of Potent Hepatitis C Virus NS3 Helicase Inhibitors Isolated from the Yellow Dyes Thioflavine S and Primuline

  摘要：

  A screen for hepatitis C virus (HCV) NS3 helicase inhibitors revealed that the commercial dye thioflavine S was the most potent inhibitor of NS3-catalyzed DNA and RNA unwinding in the 827-compound National Cancer Institute Mechanistic Set. Thioflavine S and the related dye primuline were separated here into their pure components, all of which were oligomers of substituted benzothiazoles. The most potent compound (P4), a benzothiazole tetramer, inhibited unwinding >50% at 2 +/- 1 mu M, inhibited the subgenomic HCV replicon at 10 mu M, and was not toxic at 100 mu M. Because P4 also interacted with DNA, more specific analogues were synthesized from the abundant dimeric component of primuline. Some of the 32 analogues prepared retained ability to inhibit HCV helicase but did not appear to interact with DNA. The most potent of these specific helicase inhibitors (compound 17) was active against the replicon and inhibited the helicase more than 50% at 2.6 +/- 1 mu M.

  DOI：

  10.1021/jm300021v

文献信息

• HCV Helicase Inhibitors and Methods of Use Thereof
  申请人：Aube Jeffrey

  公开号：US20140227225A1

  公开（公告）日：2014-08-14

  The present invention discloses thioflavine S and primuline derivatives which inhibit hepatitis C virus helicase and protease activity. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are useful as antiviral agents. The present invention further relates to pharmaceutical compositions containing the aforementioned compounds and methods of treating an HCV infection.

  本发明揭示了硫黄荧光素S和初黄素衍生物，其抑制丙型肝炎病毒的解旋酶和蛋白酶活性。因此，本发明的化合物干扰了丙型肝炎病毒的生命周期，并可用作抗病毒剂。本发明还涉及含有上述化合物的制药组合物和治疗HCV感染的方法。
• US9464064B2
  申请人：——

  公开号：US9464064B2

  公开（公告）日：2016-10-11
• Optimization of Potent Hepatitis C Virus NS3 Helicase Inhibitors Isolated from the Yellow Dyes Thioflavine S and Primuline
  作者：Kelin Li、Kevin J. Frankowski、Craig A. Belon、Ben Neuenswander、Jean Ndjomou、Alicia M. Hanson、Matthew A. Shanahan、Frank J. Schoenen、Brian S. J. Blagg、Jeffrey Aubé、David N. Frick

  DOI：10.1021/jm300021v

  日期：2012.4.12

  A screen for hepatitis C virus (HCV) NS3 helicase inhibitors revealed that the commercial dye thioflavine S was the most potent inhibitor of NS3-catalyzed DNA and RNA unwinding in the 827-compound National Cancer Institute Mechanistic Set. Thioflavine S and the related dye primuline were separated here into their pure components, all of which were oligomers of substituted benzothiazoles. The most potent compound (P4), a benzothiazole tetramer, inhibited unwinding >50% at 2 +/- 1 mu M, inhibited the subgenomic HCV replicon at 10 mu M, and was not toxic at 100 mu M. Because P4 also interacted with DNA, more specific analogues were synthesized from the abundant dimeric component of primuline. Some of the 32 analogues prepared retained ability to inhibit HCV helicase but did not appear to interact with DNA. The most potent of these specific helicase inhibitors (compound 17) was active against the replicon and inhibited the helicase more than 50% at 2.6 +/- 1 mu M.