4-chloro-3-(4-chloro-benzoylamino)-benzoic acid

• 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: 4-chloro-3-(4-chloro-benzoylamino)-benzoic acid
• 英文别名: 4-chloro-3-[(4-chlorobenzoyl)amino]benzoic acid
• 化学式: C₁₄H₉Cl₂NO₃
• 分子量: 310.136
• InChiKey: FYGZXGAITYOBRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chloro-3-(4-chloro-benzoylamino)-benzoic acid 在 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 3-(4-chlorobenzamido)-4-chlorobenzohydroxamate
  参考文献：
  名称：

  Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from Schistosoma mansoni for the Treatment of Schistosomiasis

  摘要：

  Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the: inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (I and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.

  DOI：

  10.1021/acs.jmedchem.5b01478
• 作为产物：
  描述：

  3-氨基-4-氯苯甲酸甲酯 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 水 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 4-chloro-3-(4-chloro-benzoylamino)-benzoic acid
  参考文献：
  名称：

  Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from Schistosoma mansoni for the Treatment of Schistosomiasis

  摘要：

  Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the: inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (I and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.

  DOI：

  10.1021/acs.jmedchem.5b01478

文献信息

• [EN] AMIDE DERIVATIVES AND THEIR USE AS CHLORIDE CHANNEL BLOCKERS<br/>[FR] DERIVES AMIDE ET LEUR UTILISATION EN TANT QU'AGENTS BLOQUANT LES CANAUX CHLORURE
  申请人：NEUROSEARCH AS

  公开号：WO2004022525A1

  公开（公告）日：2004-03-18

  The present invention relates to novel amide derivatives useful as chloride channel blockers. In other aspects the invention relates to the use of these compounds in a method for therapy, such as for the treatment of bone metabolic diseases, diseases responsive to modulation of the mast cell or basophil activity, diseases responsive to inhibition of angiogenesis, or sickle cell anaemia, and to pharmaceutical compositions comprising the compounds of the invention.

  本发明涉及作为氯离子通道阻滞剂有用的新型酰胺衍生物。在其他方面，本发明涉及将这些化合物用于治疗方法，例如用于治疗骨代谢性疾病、对肥大细胞或嗜碱性粒细胞活性调节敏感的疾病、对血管生成抑制敏感的疾病或镰刀细胞贫血，以及包括本发明化合物的药物组合物。
• Pyridopyrimidinone Inhibitors of PIM-1 and/or PIM-3
  申请人：Kearney Patrick

  公开号：US20090042918A1

  公开（公告）日：2009-02-12

  Compounds of formula (I), useful for inhibiting PIM-I and/or PIM-3: and pharmaceutically acceptable salts thereof, wherein Y, Z, R 1 , R 3 , Q, X and R 4 are as defined above. Pharmaceutical compositions and methods of treating diseases and conditions, such as cancer, are also disclosed.

  式(I)的化合物，用于抑制PIM-I和/或PIM-3：及其药学上可接受的盐，其中Y，Z，R1，R3，Q，X和R4如上所定义。还公开了药物组合物和治疗疾病和病症（如癌症）的方法。
• US8053454B2
  申请人：——

  公开号：US8053454B2

  公开（公告）日：2011-11-08
• Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from <i>Schistosoma mansoni</i> for the Treatment of Schistosomiasis
  作者：Tino Heimburg、Alokta Chakrabarti、Julien Lancelot、Martin Marek、Jelena Melesina、Alexander-Thomas Hauser、Tajith B. Shaik、Sylvie Duclaud、Dina Robaa、Frank Erdmann、Matthias Schmidt、Christophe Romier、Raymond J. Pierce、Manfred Jung、Wolfgang Sippl

  DOI：10.1021/acs.jmedchem.5b01478

  日期：2016.3.24

  Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the: inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (I and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.