2-(2,2,2-trifluoroacetylamino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylic acid (3-chlorophenyl)amide

• 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-(2,2,2-trifluoroacetylamino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylic acid (3-chlorophenyl)amide
• 英文别名: N-(3-chlorophenyl)-2-[(trifluoroacetyl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide；N-(3-chlorophenyl)-2-[(2,2,2-trifluoroacetyl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide
• 化学式: C₁₈H₁₆ClF₃N₂O₂S
• mdl: MFCD01177195
• 分子量: 416.851
• InChiKey: IWADIEZHUMJRFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  86.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(3-氯-苯基)-2-氰基-乙酰胺 在 吗啉 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 Glauber's salt 、 ammonium acetate 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 6.0h， 生成 2-(2,2,2-trifluoroacetylamino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylic acid (3-chlorophenyl)amide
  参考文献：
  名称：

  Optimization of 2-Acylaminocycloalkylthiophene Derivatives for Activity against Staphylococcus aureus RnpA

  摘要：

  金黄色葡萄球菌被广泛认为会引起难以治疗的细菌感染，因为抗生素耐药性的出现。因此，有必要开发新的抗菌药物来治疗金黄色葡萄球菌疾病。为此，金黄色葡萄球菌RnpA是一种必不可少的酶，据推测参与两个必需的细胞过程，前体tRNA（ptRNA）成熟和mRNA降解。相应的高通量筛选活动已经确定苯基氨基环硫烯为一种RnpA抑制剂的化学类，通过降低RnpA ptRNA和mRNA降解活性以及低人类细胞毒性显示出有希望的抗菌效果。在这里，我们进行了化学骨架的结构活性关系研究。结果显示，环烷烃环大小和三氟乙酰胺基团对抗菌活性是必需的，而对药效团苯基的对位和/或间位的修饰允许调节骨架的抗微生物性能和RnpA抑制活性。在抗微生物活性方面表现最佳的化合物在浓度高达100 µM时也没有对人类细胞系表现出细胞毒性，这比最低抑菌浓度（MIC）高出100倍。对一种类似物RNP0012的重点研究显示，该化合物减少了在金黄色葡萄球菌疾病小鼠模型中的细菌负担。综合而言，所呈现的结果预计将为优化下一代RnpA抑制剂类似物的早期框架提供基础，这些类似物可能代表新一类抗菌药物的前体。

  DOI：

  10.3390/antibiotics10040369

文献信息

• Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A)
  作者：Eric C. Truong、Puay W. Phuan、Amanda L. Reggi、Loretta Ferrera、Luis J. V. Galietta、Sarah E. Levy、Alannah C. Moises、Onur Cil、Elena Diez-Cecilia、Sujin Lee、Alan S. Verkman、Marc O. Anderson

  DOI：10.1021/acs.jmedchem.7b00020

  日期：2017.6.8

  Transmembrane protein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a calcium-activated chloride channel expressed widely mammalian cells, including epithelia, vascular smooth muscle tissue, electrically excitable cells, and some tumors. TMEM16A inhibitors have been proposed for treatment of disorders of epithelial fluid and mucus secretion, hypertension, asthma, and possibly cancer. Herein we report, by screening, the discovery of 2-acylaminocycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as inhibitors of TMEM16A and analysis of 48 synthesized analogs (10ab-10bw) of the original AACT compound (10aa). Structure activity studies indicated the importance of benzene substituted as 2- or 4-methyl, or 4-fluoro, and defined the significance of thiophene substituents and size of the cycloalkylthiophene core. The most potent compound (10bm), which contains an unusual bromodifluoroacetamide at the thiophene 2-position, had IC50 of similar to 30 nM, similar to 3.6-fold more potent than the most potent previously reported TMEM16A inhibitor 4 (Ani9), and >10-fold improved metabolic stability. Direct and reversible inhibition of TMEM16A by 10bm was demonstrated by patch-clamp analysis. AACTs may be useful as pharmacological tools to study TMEM16A function and as potential drug development candidates.
• WO2006/44826
  申请人：——

  公开号：——

  公开（公告）日：——
• THIOPHENS AND THEIR USE AS ANTI-TUMOR AGENTS
  申请人：Compass Pharmaceuticals LLC

  公开号：EP1802634A2

  公开（公告）日：2007-07-04
• Thiophens and Their Use as Anti-Tumor Agents
  申请人：Ward John

  公开号：US20090143411A1

  公开（公告）日：2009-06-04

  The present invention provides novel compounds and pharmaceutical compositions thereof, as well as methods for using the compounds and pharmaceutical compositions for treating tumors. Examples of specific tumor types that the compounds may be used to treat include, but are not limited to sarcomas, melanomas, neuroblastomas, carcinomas (including but not limited to lung, renal cell, ovarian, liver, bladder, and pancreatic carcinomas), and mesotheliomas.
• [EN] COMPOSITIONS AND THEIR USE AS ANTI-TUMOR AGENTS<br/>[FR] COMPOSITIONS ET LEUR UTILISATION EN TANT QU'AGENTS ANTITUMORAUX
  申请人：COMPASS PHARMACEUTICALS LLC

  公开号：WO2006044826A2

  公开（公告）日：2006-04-27

  [EN] The present invention provides novel compounds and pharmaceutical compositions thereof, as well as methods for using the compounds and pharmaceutical compositions for treating tumors. Examples of specific tumor types that the compounds may be used to treat include, but are not limited to sarcomas, melanomas, neuroblastomas, carcinomas (including but not limited to lung, renal cell, ovarian, liver, bladder, and pancreatic carcinomas), and mesotheliomas.
  [FR] L'invention concerne de nouveaux composés et des compositions pharmaceutiques comportant ces nouveaux composés, ainsi que des méthodes pour utiliser les composés et les compositions pharmaceutiques de l'invention pour traiter des tumeurs. Des exemples de types de tumeur spécifiques pouvant être traités par l'utilisation des composés de l'invention comprennent, de manière non exhaustive: les sarcomes, les mélanomes, les neuroblastomes, les carcinomes (comprenant, de manière non exhaustive, les carcinomes de poumons, des cellules rénales, des ovaires, du foie, de la vessie et du pancréas), et des mésothéliomes.