polyglutamine aggregation inhibitor III | 300670-16-0

• 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: polyglutamine aggregation inhibitor III
• 英文别名: C2-8；3-(N-(4-bromophenyl)sulfamoyl)-N-(4-bromophenyl)benzamide；N-(4-bromo-phenyl)-3-(4-bromo-phenylsulfamoyl)benzamide；N-(4-bromophenyl)-3-[(4-bromophenyl)sulfamoyl]benzamide
• CAS: 300670-16-0
• 化学式: C₁₉H₁₄Br₂N₂O₃S
• 分子量: 510.206
• InChiKey: SJJKUNDBFWUAQB-UHFFFAOYSA-N

物化性质

• 密度：
  1.760±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：~20 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2935009090

反应信息

• 作为反应物：
  描述：

  3-溴丙烯 、 polyglutamine aggregation inhibitor III 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 3-(N-allyl-N-(4-bromophenyl)sulfamoyl)-N-(4-bromophenyl)benzamide
  参考文献：
  名称：

  3-(N-Arylsulfamoyl)benzamides, inhibitors of human sirtuin type 2 (SIRT2)

  摘要：

  Inhibition of sirtuin 2 (SIRT2) is known to be protective against the toxicity of disease proteins in Parkinson's and Huntington's models of neurodegeneration. Previously, we developed SIRT2 inhibitors based on the 3-(N-arylsulfamoyl)benzamide scaffold, including3-(N-(4-bromophenyl)sulfamoyl)-N-(4-bromophenyl) benzamide(C2-8, 1a), which demonstrated neuroprotective effects in a Huntington's mouse model, but had low potency of SIRT2 inhibition. Here we report that N-methylation of 1a greatly increases its potency and results in excellent selectivity for SIRT2 over SIRT1 and SIRT3 isoforms. Structure-activity relationships observed for 1a analogs and docking simulation data suggest that the para-substituted amido moiety of these compounds could occupy two potential hydrophobic binding pockets in SIRT2. These results provide a direction for the design of potent drug-like SIRT2 inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.089
• 作为产物：
  描述：

  4-溴苯胺 、 3-[(4-bromophenyl)carbamoyl]benzenesulfonyl chloride 以 乙腈 为溶剂， 生成 polyglutamine aggregation inhibitor III
  参考文献：
  名称：

  Tarasov; Moskvichev; Timoshenko, Russian Journal of Organic Chemistry, 2000, vol. 36, # 1, p. 69 - 71

  摘要：

  DOI：

文献信息

• Benzamide Compounds and Related Methods of Use
  申请人：Northwestern University

  公开号：US20150025235A1

  公开（公告）日：2015-01-22

  Benzamide compounds and derivatives thereof, as can be used for selective inhibition of the SIRT2 enzyme and/or therapeutic use in the treatment of Huntington's disease.

  苯甲酰胺化合物及其衍生物可用于选择性抑制SIRT2酶和/或治疗亨廷顿病。
• Compositions and methods for modulating interaction between polypeptides
  申请人：Kazantsev G. Aleksey

  公开号：US20050239833A1

  公开（公告）日：2005-10-27

  The present invention is based, in part, on assays we conducted that revealed compounds that may be used to treat or prevent diseases characterized by an abnormal or undesirable association of one protein with another.

  本发明部分基于我们所进行的检测，这些检测揭示了可用于治疗或预防以一种蛋白质与另一种蛋白质的异常或不良结合为特征的疾病的化合物。
• DRUG COMBINATIONS TO TREAT HYPERPROLIFERATIVE DISORDERS
  申请人：Maurer Barry James

  公开号：US20100035911A1

  公开（公告）日：2010-02-11

  A method of treating a hyperproliferative disorder, including a cancer, in a subject in need of such treatment, comprising administering to said subject a pharmaceutical combination containing a treatment effective amount of: (a) a vitamin A derivative (i.e., a retinoid), or a pharmaceutically acceptable salt thereof, and an inhibitor of microtubule structure or function; or (b) a combination containing fenretinide (i.e., N-(4-hydrophenyl) retinamide, 4-HPR) and ABT-751 (i.e., N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonamide). Vitamin A derivatives that may be useful for this invention according to (a) include, but are not limited to, all-trans-retinoic acid, 13-cis-retinoic acid, and fenretinide. Microtubule inhibitors that may be useful for this invention according to (a) include, but are not limited to, inhibitors of the Vinca binding domain (e.g., vincristine, vinblastine, vinorelbine, and cryptophycin 52), inhibitors of the Taxane domain (e.g., paclitaxel, docetaxel, and epothilones), and inhibitors of the colchicine site (e.g., colchicine, ABT-751, CI-980, and combretastatin). A preferred retinoid according to (a) is fenretinide. A preferred microtubule inhibitor according to (b) is ABT-751.
• COMPOSITIONS AND METHODS FOR MODULATING INTERACTION BETWEEN POLYPEPTIDES
  申请人：The General Hospital Corporation

  公开号：US20130203733A1

  公开（公告）日：2013-08-08

  The present invention is based, in part, on assays we conducted that revealed compounds that may be used to treat or prevent diseases characterized by an abnormal or undesirable association of one protein with another.
• US8404747B2
  申请人：——

  公开号：US8404747B2

  公开（公告）日：2013-03-26