1-(3-fluoro-4-methoxybenzyl)piperazine | 523980-18-9

• 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: 1-(3-fluoro-4-methoxybenzyl)piperazine
• 英文别名: 1-[(3-Fluoro-4-methoxyphenyl)methyl]piperazine
• CAS: 523980-18-9
• 化学式: C₁₂H₁₇FN₂O
• mdl: MFCD05189160
• 分子量: 224.278
• InChiKey: DOHKJEHZIZZYLD-UHFFFAOYSA-N

物化性质

• 沸点：
  319.2±37.0 °C(Predicted)
• 密度：
  1.120±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-fluoro-4-methoxybenzyl)piperazine 、 1-propyl-8-[4-[[[p-nitrophenyl]oxy]sulfonyl]phenyl]xanthine 以 二甲基亚砜 为溶剂， 反应 3.0h， 以49%的产率得到8-(4-((4-(3-fluoro-4-methoxybenzyl)piperazin-1-yl)sulfonyl)phenyl)-1-propyl-3,7-dihydropurine-2,6-dione
  参考文献：
  名称：

  A_2B Adenosine Receptor Antagonists with Picomolar Potency

  摘要：

  The A(2B) adenosine receptor (A(2B)AR) was proposed as a novel target for the (immuno)therapy of cancer since A(2B)AR blockade results in antiproliferative, antiangiogenic, antimetastatic, and immunostimulatory effects. In this study, we explored the structure-activity relationships of xanthin-8-yl-benzenesulfonamides mainly by introducing a variety of linkers and substituents attached to the sulfonamide residue. A new, convergent strategy was established, which facilitated the synthesis of the target compounds. Many of the new compounds exhibited subnanomolar affinity for the A(2B)AR combined with high selectivity. Functional groups were introduced, which will allow the attachment of dyes and other reporter groups. 8-(4((4-(4-Bromophenyl)piperazin-1-yl)sulfonyl)phenyl)-1-propylxanthine (34, PSB-1901) was the most potent A(2B)-antagonist (K-i 0.0835 nM, K-B 0.0598 nM, human A(2B)AR) with >10 000-fold selectivity versus all other AR subtypes. It was similarly potent and selective at the mouse A(2B)AR, making it a promising tool for preclinical studies. Computational studies predicted halogen bonding to contribute to the outstanding potency of 34.

  DOI：

  10.1021/acs.jmedchem.9b00071
• 作为产物：
  描述：

  tert-butyl 4-(3-fluoro-4-methoxybenzyl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以92%的产率得到1-(3-fluoro-4-methoxybenzyl)piperazine
  参考文献：
  名称：

  A_2B Adenosine Receptor Antagonists with Picomolar Potency

  摘要：

  The A(2B) adenosine receptor (A(2B)AR) was proposed as a novel target for the (immuno)therapy of cancer since A(2B)AR blockade results in antiproliferative, antiangiogenic, antimetastatic, and immunostimulatory effects. In this study, we explored the structure-activity relationships of xanthin-8-yl-benzenesulfonamides mainly by introducing a variety of linkers and substituents attached to the sulfonamide residue. A new, convergent strategy was established, which facilitated the synthesis of the target compounds. Many of the new compounds exhibited subnanomolar affinity for the A(2B)AR combined with high selectivity. Functional groups were introduced, which will allow the attachment of dyes and other reporter groups. 8-(4((4-(4-Bromophenyl)piperazin-1-yl)sulfonyl)phenyl)-1-propylxanthine (34, PSB-1901) was the most potent A(2B)-antagonist (K-i 0.0835 nM, K-B 0.0598 nM, human A(2B)AR) with >10 000-fold selectivity versus all other AR subtypes. It was similarly potent and selective at the mouse A(2B)AR, making it a promising tool for preclinical studies. Computational studies predicted halogen bonding to contribute to the outstanding potency of 34.

  DOI：

  10.1021/acs.jmedchem.9b00071

文献信息

• ACTIVATOR OF ADIPONECTIN RECEPTOR
  申请人：THE UNIVERSITY OF TOKYO

  公开号：US20160214967A1

  公开（公告）日：2016-07-28

  An AdipoR activator for activating both AdipoR1 and AdipoR2 is provided. A compound represented by the following formula (1), wherein A is a substituted or unsubstituted aryl group or the like, Y 1 is (CHR 2 ) a — or the like, X is CH or N, R 1 is a C 1-7 alkyl group, m is an integer of 0-4, Y 2 is *—O—CH 2 —CONH—, *—CONH—(CH 2 ) b —CO— or the like, Z is a cyclic group, B may be a substituent of the cyclic group represented by Z, and n is an integer of 0-3.

  提供了一种用于激活AdipoR1和AdipoR2的AdipoR激活剂。以下式（1）表示的化合物，其中A是取代或未取代的芳基或类似物，Y1是（CHR2）a—或类似物，X是CH或N，R1是C1-7烷基基团，m是0-4的整数，Y2是*—O—CH2—CONH—，*—CONH—（ ）b—CO—或类似物，Z是环基团，B可以是Z代表的环基团的取代基，n是0-3的整数。
• Substituted 4,5,6,7-tetrahydrobenzthiazol-2-ylamine compounds
  申请人：Oberboersch Stefan

  公开号：US20070027315A1

  公开（公告）日：2007-02-01

  Substituted 4,5,6,7-tetrahydrobenzothiazol-2-ylamine compounds, a method for their production; pharmaceutical compositions comprising them, and methods of use for modulating biological functions and/or treating or inhibiting various medical conditions such as, e.g., depression and pain.

  4,5,6,7-四氢苯并噻唑-2-胺化合物的替代物，其生产方法；包括它们的药物组合物，以及用于调节生物功能和/或治疗或抑制各种医疗状况（如抑郁症和疼痛等）的使用方法。
• Cyclohexyl-1, 4-diamine compounds
  申请人：Sundermann Corinna

  公开号：US20070112007A1

  公开（公告）日：2007-05-17

  Novel cyclohexyl-1,4-diamine compounds corresponding to formula I, processes for the production thereof, pharmaceutical compositions containing these compounds, methods of producing pharmaceutical compositions including these compounds and related methods of treating or inhibiting certain diseases or conditions.

  新型环己基-1,4-二胺化合物对应于式I，其生产方法，包含这些化合物的药物组合物，制备包含这些化合物的药物组合物的方法以及相关的治疗或抑制某些疾病或状况的方法。
• Discovery of proteolysis-targeting chimera targeting undruggable proteins using a covalent ligand screening approach
  作者：Hyeonjun Lee、Ju Yeon Lee、Hyunsoo Jang、Hye Young Cho、Minhee Kang、Sang Hyun Bae、Suin Kim、Eunji Kim、Jaebong Jang、Jin Young Kim、Young Ho Jeon

  DOI：10.1016/j.ejmech.2023.115929

  日期：2024.1

  Targeted protein degradation (TPD) technology, such as proteolysis-targeting chimera (PROTAC), has become a new therapeutic modality. However, the degradation of undruggable proteins, such as those involved in protein-protein interactions (PPIs), using PROTAC is still limited owing to the difficulties in finding small-molecule binders of these proteins. To identify new chemical moieties that bind to

  靶向蛋白降解（TPD）技术，例如蛋白水解靶向嵌合体（PROTAC），已成为一种新的治疗方式。然而，由于难以找到这些蛋白质的小分子结合物，使用 PROTAC 降解不可成药的蛋白质，例如那些参与蛋白质-蛋白质相互作用 (PPI) 的蛋白质，仍然受到限制。为了识别与目标蛋白 (POI) 靶位点结合的新化学部分，我们使用液相色谱-串联质谱 (LC-MS/MS) 进行了位点特异性和基于片段的共价配体筛选。为了将选定的命中应用于 PROTAC 方法，进行了二维 (2D) 核磁共振 (NMR) 实验，以评估其类似物在没有共价弹头的情况下的可逆结合。为了证明所提出的方法，选择人鼠双分钟 (MDM)2 作为模型系统，因为它涉及 PPI 并且已知是可降解的靶蛋白。蛋白质印迹分析表明，新合成的 PROTAC 掺入了筛选命中的可逆类似物，以剂量和时间依赖性方式影响降解。这种方法使得使用 PROTAC 技术来开发以前不可成药的蛋白质来治疗
• SUBSTITUIERTE 4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YLAMIN-VERBINDUNGEN
  申请人：Grünenthal GmbH

  公开号：EP1716128B1

  公开（公告）日：2010-03-31