ACP1b | 1371635-83-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: ACP1b
• 英文别名: ACP1a；2-methyl-N-(3-phenylpropyl)-2-[5-(trifluoromethyl)pyridin-2-yl]sulfonylpropanamide
• CAS: 1371635-83-4
• 化学式: C₁₉H₂₁F₃N₂O₃S
• 分子量: 414.449
• InChiKey: IEAIZTCYBFPLPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  84.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)sulfonyl)propanoic acid 、 3-苯基-1-丙胺 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以88%的产率得到ACP1b
  参考文献：
  名称：

  [EN] ACTIVATORS OF CYLINDRICAL PROTEASES
  [FR] ACTIVATEURS DES PROTÉASES CYLINDRIQUES

  摘要：

  本发明涉及圆柱形蛋白酶（“ACPs”）的激活剂，特别是ClpP，以及其在细菌感染的诊断和治疗中的作用。已经确定了许多激活酪蛋白酶P（“ClpP”）的ACP，独立地只能降解小肽。在存在ACP的情况下，ClpP可以被激活，使其能够降解更大的蛋白质，从而消除了ATP依赖的分子伴侣引起的特异性。发现了ACP成员具有杀菌活性。因此，ACP代表了一类新的化合物，可以激活ClpP，并可以作为潜在的新型抗生素开发。

  公开号：

  WO2012079164A1

文献信息

• Synthesis and Antichlamydial Activity of Molecules Based on Dysregulators of Cylindrical Proteases
  作者：Mohamed A. Seleem、Nathalia Rodrigues de Almeida、Yashpal Singh Chhonker、Daryl J. Murry、Zaira da Rosa Guterres、Amanda M. Blocker、Shiomi Kuwabara、Derek J. Fisher、Emilse S. Leal、Manuela R. Martinefski、Mariela Bollini、María Eugenia Monge、Scot P. Ouellette、Martin Conda-Sheridan

  DOI：10.1021/acs.jmedchem.0c00371

  日期：2020.4.23

  there is no FDA-approved treatment specific for chlamydial infections. We recently reported two sulfonylpyridines that halt the growth of the pathogen. Herein, we present a SAR of the sulfonylpyridine molecule by introducing substituents on the aromatic regions. Biological evaluation studies showed that several analogues can impair the growth of C. trachomatis without affecting host cell viability. The

  沙眼衣原体是全球最常见的性传播细菌性疾病，也是世界上不孕症和可预防的感染性失明（沙眼）的主要原因。不幸的是，FDA 还没有批准针对衣原体感染的治疗方法。我们最近报道了两种磺酰吡啶可以阻止病原体的生长。在这里，我们通过在芳香区引入取代基来展示磺酰吡啶分子的SAR。生物学评价研究表明，几种类似物可以损害沙眼衣原体的生长而不影响宿主细胞的活力。这些化合物不会杀死其他细菌，表明对衣原体具有选择性。这些化合物对哺乳动物细胞系表现出轻微的毒性。在果蝇测定中发现这些化合物不具有致突变性，并且在血浆和胃液中表现出良好的稳定性。所呈现的结果表明该支架是开发选择性抗衣原体药物的一个有希望的起点。
• Activators of Cylindrical Proteases as Antimicrobials: Identification and Development of Small Molecule Activators of ClpP Protease
  作者：Elisa Leung、Alessandro Datti、Michele Cossette、Jordan Goodreid、Shannon E. McCaw、Michelle Mah、Alina Nakhamchik、Koji Ogata、Majida El Bakkouri、Yi-Qiang Cheng、Shoshana J. Wodak、Bryan T. Eger、Emil F. Pai、Jun Liu、Scott Gray-Owen、Robert A. Batey、Walid A. Houry

  DOI：10.1016/j.chembiol.2011.07.023

  日期：2011.9

  CIpP is a cylindrical serine protease whose ability to degrade proteins is regulated by the unfoldase ATP-dependent chaperones. CIpP on its own can only degrade small peptides. Here, we used CIpP as a target in a high-throughput screen for compounds, which activate the protease and allow it to degrade larger proteins, hence, abolishing the specificity arising from the ATP-dependent chaperones. Our screen resulted in five distinct compounds, which we designate as Activators of Self-Compartmentalizing Proteases 1 to 5 (ACP1 to 5). The compounds are found to stabilize the CIpP double-ring structure. The ACP1 chemical structure was considered to have drug-like characteristics and was further optimized to give analogs with bactericidal activity. Hence, the ACPs represent classes of compounds that can activate CIpP and that can be developed as potential novel antibiotics.
• TREATMENTS FOR MYCOBACTERIUM TUBERCULOSIS
  申请人：PRESIDENT AND FELLOWS OF HARVARD COLLEGE

  公开号：US20140243255A1

  公开（公告）日：2014-08-28

  The technology described herein relates to treatments for tuberculosis which target the ClpP1P2 protease complex, including ClpC1. Further embodiments relate to assays and screens for modulators of the ClpP1P2 protease complex, including ClpC1.
• US9925251B2
  申请人：——

  公开号：US9925251B2

  公开（公告）日：2018-03-27
• [EN] TREATMENTS FOR MYCOBACTERIUM TUBERCULOSIS<br/>[FR] TRAITEMENTS POUR MYCOBACTERIUM TUBERCULOSIS
  申请人：HARVARD COLLEGE

  公开号：WO2013059622A1

  公开（公告）日：2013-04-25

  The technology described herein relates to treatments for tuberculosis which target the ClpPlP2 protease complex, including ClpCl. Further embodiments relate to assays and screens for modulators of the ClpPlP2 protease complex, including ClpCl.