ACP1a | 1371635-84-5

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: ACP1a
• 英文别名: ACP1b；N-{2-[(2-chlorophenyl)sulfanyl]ethyl}-2-methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]sulfonyl}propanamide；N-[2-(2-chlorophenyl)sulfanylethyl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]sulfonylpropanamide
• CAS: 1371635-84-5
• 化学式: C₁₈H₁₈ClF₃N₂O₃S₂
• 分子量: 466.933
• InChiKey: OUZIIFOEMPAZKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-((2-chlorophenyl)thio)ethan-1-amine 、 2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)thio)propanoic acid 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， 生成 ACP1a
  参考文献：
  名称：

  Activators of Cylindrical Proteases as Antimicrobials: Identification and Development of Small Molecule Activators of ClpP Protease

  摘要：

  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.

  DOI：

  10.1016/j.chembiol.2011.07.023

文献信息

• [EN] ACTIVATORS OF CYLINDRICAL PROTEASES<br/>[FR] ACTIVATEURS DES PROTÉASES CYLINDRIQUES
  申请人：UNIV TORONTO

  公开号：WO2012079164A1

  公开（公告）日：2012-06-21

  The present invention is directed to activators of cylindrical proteases ("ACPs"), particularly ClpP, and the role thereof in the diagnosis and treatment of bacterial infections. A number of ACPs were identified that activate caseinolytic protease P ("ClpP"), which independently can only degrade small peptides. In the presence of ACPs, ClpP may be activated to allow it to degrade larger proteins, hence, abolishing the specificity arising from the ATP-dependent chaperones. Members of the ACPs were found to have bactericidal activity. As such, ACPs represent a new classes of compounds that can activate ClpP and that can be developed as potential novel antibiotics.

  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。
• 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.
• 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.