N-[1-(3,4-dichlorobenzyl)piperidin-4-yl]-(6-amino-2-benzothiazolylthio)acetamide | 290363-23-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-[1-(3,4-dichlorobenzyl)piperidin-4-yl]-(6-amino-2-benzothiazolylthio)acetamide
• 英文别名: 2-[(6-amino-2-benzothiazolyl)thio]-N-[1-[(3,4-dichlorophenyl)methyl]-4-piperidinyl]acetamide；Banyu (I)；2-[(6-Amino-1,3-benzothiazol-2-yl)sulfanyl]-N-{1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl}acetamide；2-[(6-amino-1,3-benzothiazol-2-yl)sulfanyl]-N-[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]acetamide
• CAS: 290363-23-4
• 化学式: C₂₁H₂₂Cl₂N₄OS₂
• 分子量: 481.47
• InChiKey: QOHFBKIKGAINLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 N-[1-(3,4-dichlorobenzyl)piperidin-4-yl]-(6-amino-2-benzothiazolylthio)acetamide 在 三乙胺 作用下， 以 氯仿 为溶剂， 反应 20.0h， 以67%的产率得到N-[1-(3,4-dichlorobenzyl)piperidin-4-yl]-(6-acetamido-2-benzothiazolylthio)acetamide
  参考文献：
  名称：

  Structure-Activity Relationships of 2-(Benzothiazolylthio)acetamide Class of CCR3 Selective Antagonist

  摘要：

  描述了新型选择性CCR3受体拮抗剂的结构-活性关系，2-(苯并噻唑基硫)乙酰胺衍生物。通过筛选基于我们的人类CCR1和CCR3受体双拮抗剂结构的专注文库，发现了一种领先结构（1a）。1a的衍生化，包括在苯并噻唑和哌啶侧链的每个苯环中引入取代基，结果识别出具有强效和选择性的化合物（1b、r、s），表现出纳摩尔结合亲和力（IC50：1.5—3.0 nM）并且对CCR3受体的选择性超过CCR1受体800倍以上。

  DOI：

  10.1248/cpb.51.697
• 作为产物：
  描述：

  4-叔丁氧羰基氨基哌啶 在 盐酸 、 三乙酰氧基硼氢化钠 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 58.17h， 生成 N-[1-(3,4-dichlorobenzyl)piperidin-4-yl]-(6-amino-2-benzothiazolylthio)acetamide
  参考文献：
  名称：

  Structure-Activity Relationships of 2-(Benzothiazolylthio)acetamide Class of CCR3 Selective Antagonist

  摘要：

  描述了新型选择性CCR3受体拮抗剂的结构-活性关系，2-(苯并噻唑基硫)乙酰胺衍生物。通过筛选基于我们的人类CCR1和CCR3受体双拮抗剂结构的专注文库，发现了一种领先结构（1a）。1a的衍生化，包括在苯并噻唑和哌啶侧链的每个苯环中引入取代基，结果识别出具有强效和选择性的化合物（1b、r、s），表现出纳摩尔结合亲和力（IC50：1.5—3.0 nM）并且对CCR3受体的选择性超过CCR1受体800倍以上。

  DOI：

  10.1248/cpb.51.697

文献信息

• Inhibition of chemokine CCL7 or receptor CCR3 of same for the treatment and diagnosis of prostate cancer
  申请人：Universite Paul Sabatier (Toulouse III)

  公开号：US10401365B2

  公开（公告）日：2019-09-03

  The invention concerns an inhibitor of the expression of chemokine CCL7 or an inhibitor of the expression of the receptor CCR3 or an inhibitor of CCL7/CCR3 interaction for the use of same to prevent or treat the extension of prostate cancer outside the prostatic capsule in a subject. The invention also concerns a method for determining the degree of aggressiveness of a prostate cancer tumor in a subject suffering from prostate cancer, comprising a step of determining the concentration or level of expression of the receptor CCR3 in a sample of prostate tumor cells obtained from said subject.

  本发明涉及一种趋化因子CCL7表达抑制剂或受体CCR3表达抑制剂或CCL7/CCR3相互作用抑制剂，用于预防或治疗受试者的前列腺癌向前列腺囊外延伸。本发明还涉及一种确定前列腺癌患者前列腺癌肿瘤侵袭程度的方法，该方法包括一个步骤，即确定从所述患者处获得的前列腺肿瘤细胞样本中受体CCR3的浓度或表达水平。
• Discovery of a novel CCR3 selective antagonist
  作者：Akira Naya、Kensuke Kobayashi、Makoto Ishikawa、Kenji Ohwaki、Toshihiko Saeki、Kazuhito Noguchi、Norikazu Ohtake

  DOI：10.1016/s0960-894x(01)00176-7

  日期：2001.5

  In searching for a novel CCR3 receptor antagonist, we designed a library that included a variety of carboxamide derivatives based on the structure of our potent antagonists for human CCR1 and CCR3 receptors, and screened the new compounds for inhibitory actitity against I-125-Eotaxin binding to human CCR3 receptors expressed in CHO cells. Among them, two 2-(benzothiazolethio)acetamide derivatives (1a and 2a) showed binding affinities with IC50 values of 750 and 1000 nM respectively, for human CCR3 receptors. These compounds (1a and 2a) also possessed weak binding affinities for human CCR1 receptors. We selected la as a lead compound for derivatization to improve in vitro potency and selectivity for CCR3 over CCR1 receptors. Derivatization of la by incorporating substituents into each benzene ring of the benzothiazole and piperidine side chain resulted in the discovery of a compound (1b) exhibiting 820-fold selectivity for CCR3 receptors (IC50 = 2.3 nM) over CCR1 receptors (IC50-1900nM). This compound (1b) also showed potent functional antagonist activity for inhibiting Eotaxin (IC50 = 27 nM)- or RANTES (IC50 = 13 nM)-induced Ca2+ increases in eosinophils. (C) 2001 Elsevier Science Ltd. All rights reserved.
• USE OF CHEMOKINE RECEPTOR AGONISTS FOR STEM CELL TRANSPLANTATION
  申请人：TAP Pharmaceutical Products, Inc.

  公开号：EP1605966A1

  公开（公告）日：2005-12-21
• Use of chemokine receptor agonists for stem cell transplantation
  申请人：Richter Rudolf

  公开号：US20070155663A1

  公开（公告）日：2007-07-05

  A medicament comprising at least one agonist of receptors selected from the group consisting of the CCR3, CCR6 or CCR8 receptor or combinations thereof and a pharmaceutically acceptable carrier.
• Inhibition of Chemokine CCL7 or Receptor CCR3 of Same for the Treatment and Diagnosis of Prostate Cancer
  申请人：Universite Paul Sabatier (Toulouse III)

  公开号：US20170131282A1

  公开（公告）日：2017-05-11

  The invention concerns an inhibitor of the expression of chemokine CCL7 or an inhibitor of the expression of the receptor CCR3 or an inhibitor of CCL7/CCR3 interaction for the use of same to prevent or treat the extension of prostate cancer outside the prostatic capsule in a subject. The invention also concerns a method for determining the degree of aggressiveness of a prostate cancer tumour in a subject suffering from prostate cancer, comprising a step of determining the concentration or level of expression of the receptor CCR3 in a sample of prostate tumour cells obtained from said subject.