{4- [4-(2-噻吩基羰基)哌嗪-1-基]苯基}胺 | 412331-95-4

• 物质功能分类: 医药中间体 - 哌嗪类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: {4- [4-(2-噻吩基羰基)哌嗪-1-基]苯基}胺
• 英文名称: (4-(4-aminophenyl)piperazin-1-yl)(thiophen-2-yl)methanone
• 英文别名: [4-(4-aminophenyl)-1-piperazinyl]thiophen-2-ylmethanone；{4-[4-(2-Thienylcarbonyl)piperazin-1-yl]phenyl}amine；[4-(4-aminophenyl)piperazin-1-yl]-thiophen-2-ylmethanone
• CAS: 412331-95-4
• 化学式: C₁₅H₁₇N₃OS
• mdl: MFCD02628406
• 分子量: 287.385
• InChiKey: WWAUNMJQFAJHAD-UHFFFAOYSA-N

物化性质

• 沸点：
  530.1±50.0 °C(Predicted)
• 密度：
  1.297±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  77.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  {4- [4-(2-噻吩基羰基)哌嗪-1-基]苯基}胺 、 3,4-二氢一异喹啉-2,3-二甲酸-2-苄酯 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-benzyl 3-(4-(4-(thiophene-2-carbonyl)piperazin-1-yl)phenylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate
  参考文献：
  名称：

  Potent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold

  摘要：

  Direct inhibition of coagulation factor Xa (FXa) carries significant promise for developing effective and safe anticoagulants. Although a large number of FXa inhibitors have been studied, each can be classified as either possessing a highly flexible or a rigid core scaffold. We reasoned that an intermediate level of flexibility will provide high selectivity for FXa considering that its active site is less constrained in comparison to thrombin and more constrained as compared to trypsin. We studied several core scaffolds including 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid for direct FXa inhibition. Using a genetic algorithm-based docking and scoring approach, a promising candidate 23 was identified, synthesized, and found to inhibit FXa with a K-i of 28 mu M. Optimization of derivative 23 resulted in the design of a potent dicarboxamide 47, which displayed a K-i of 135 nM. Dicarboxamide 47 displayed at least 1852-fold selectivity for FXa inhibition over other coagulation enzymes and doubled PT and aPTT of human plasma at 17.1 mu M and 20.2 mu M, respectively, which are comparable to those of clinically relevant agents. Dicarboxamide 47 is expected to serve as an excellent lead for further anticoagulant discovery. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.032
• 作为产物：
  描述：

  1-(4-硝基苯基)哌嗪 在 盐酸 、 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 {4- [4-(2-噻吩基羰基)哌嗪-1-基]苯基}胺
  参考文献：
  名称：

  Potent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold

  摘要：

  Direct inhibition of coagulation factor Xa (FXa) carries significant promise for developing effective and safe anticoagulants. Although a large number of FXa inhibitors have been studied, each can be classified as either possessing a highly flexible or a rigid core scaffold. We reasoned that an intermediate level of flexibility will provide high selectivity for FXa considering that its active site is less constrained in comparison to thrombin and more constrained as compared to trypsin. We studied several core scaffolds including 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid for direct FXa inhibition. Using a genetic algorithm-based docking and scoring approach, a promising candidate 23 was identified, synthesized, and found to inhibit FXa with a K-i of 28 mu M. Optimization of derivative 23 resulted in the design of a potent dicarboxamide 47, which displayed a K-i of 135 nM. Dicarboxamide 47 displayed at least 1852-fold selectivity for FXa inhibition over other coagulation enzymes and doubled PT and aPTT of human plasma at 17.1 mu M and 20.2 mu M, respectively, which are comparable to those of clinically relevant agents. Dicarboxamide 47 is expected to serve as an excellent lead for further anticoagulant discovery. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.032

文献信息

• Novel aminophenyl piperazine or aminophenyl piperidine derivatives inhibiting prenyl transferase proteins and method for preparing same
  申请人：——

  公开号：US20040092524A1

  公开（公告）日：2004-05-13

  The invention concerns compounds corresponding to general formula (I), wherein, in particular: W represents hydrogen, COR 6 , CSR 6 , SO 2 R 6 , CO(CH 2 ) n R 6 , (CH 2 ) n R 7 ; X represents CH or N; Y represents (CH 2 ) n , CO, CH 2 CO, CH═CHCO, CH 2 CH 2 CO; Z represents a heterocycle. When Z=pyridine, then Y is other than CO. R 1 represents hydrogen, C 1 -C 6 alkyl, halogen OCH 3 , CF 3 ; R 2 and R 3 , identical or different, represent hydrogen, C 1 -C 6 alkyl; R 4 represents a) hydrogen, b) C 1 -C 6 alkyl, c) an aryl, d) a heterocycle; R 5 represents hydrogen, COR 7 R 8 , SO 2 R 7 , CO(CH 2 ) n SR 7 , CO(CH 2 ) n OR 7 , CONR 7 R 8 , CO(CH 2 ) m COR 7 ; R 6 represents a) a phenyl or a naphthyl, b) a C 1 -C 6 alkyl, a cycloalkyl, c) a heterocycle, d) NR 7 R 8 ; R 7 and R 8 , identical or different, represent a) hydrogen, C 1 -C 15 alkyl, b) a heterocycle, c) an aryl; n represents 0 to 10; m represents 2 to 10; provided that when Z represents a quinozaline or benzimidazole group, then R 5 is other than CH 2 Ph or methyl and n is other than zero. 1

  该发明涉及与一般式（I）相对应的化合物，其中，特别是：W代表氢，COR6，CSR6，SO2R6，CO（CH2）nR6，（ ）nR7；X代表CH或N；Y代表（ ）n，CO， CO，CH═CHCO， CO；Z代表杂环。当Z=吡啶时，Y不是CO。R1代表氢，C1-C6烷基，卤素OCH3，CF3；R2和R3，相同或不同，代表氢，C1-C6烷基；R4代表a）氢，b）C1-C6烷基，c）芳基，d）杂环；R5代表氢，COR7R8，SO2R7，CO（ ）nSR7，CO（ ）nOR7，CONR7R8，CO（ ）mCOR7；R6代表a）苯基或萘基，b）C1-C6烷基，环烷基，c）杂环，d）NR7R8；R7和R8，相同或不同，代表a）氢，C1-C15烷基，b）杂环，c）芳基；n表示0到10；m表示2到10；前提是当Z代表喹唑啉或苯并咪唑基团时，R5不是 Ph或甲基，n不是零。
• [EN] SMALL MOLECULE ACTIVATORS OF INTERFERON REGULATORY FACTOR 3 AND METHODS OF USE THEREOF<br/>[FR] ACTIVATEURS À PETITES MOLÉCULES DU FACTEUR 3 DE RÉGULATION DE L'INTERFÉRON ET LEURS PROCÉDÉS D'UTILISATION
  申请人：NEURALEXO INC

  公开号：WO2021226129A1

  公开（公告）日：2021-11-11

  Small molecule activators of interferon regulatory factor (IRF), such as IRF3, and methods of use are provided. In particular, compositions and methods for upregulating interferon regulatory factor 3 (IRF3) activity, such as in the brain following stroke to provide potent protection against ischemic brain injury, to improve a therapeutic time window for providing treatments to stroke patients and/or for enhancement of vaccine platforms are disclosed.

  本发明提供了干扰素调节因子（IRF）的小分子激活剂，例如IRF3，以及使用方法。具体地，本发明揭示了用于上调干扰素调节因子3（IRF3）活性的组合物和方法，例如在中风后的大脑中，以提供强大的保护作用，改善为中风患者提供治疗时间窗口和/或增强疫苗平台的治疗效果。
• DERIVES D'AMINOPHENYLE PIPERAZINE OU D'AMINO PHENYLE PIPERIDINE INHIBITEURS DE PROTEINES PRENYL TRANSFERASE
  申请人：PIERRE FABRE MEDICAMENT

  公开号：EP1324999A1

  公开（公告）日：2003-07-09
• METHODS AND COMPOUNDS FOR REGULATING APOPTOSIS
  申请人：Reed John C.

  公开号：US20090118135A1

  公开（公告）日：2009-05-07

  An assay for determining compounds that inhibit activity of a BCl-2 protein, or affect conversion of Bcl-2 from an antiapoptotic to a proapoptotic form are described. In addition, compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and related Bcl-2 family members are identified.
• [EN] NOVEL AMINOPHENYL PIPERAZINE OR AMINOPHENYL PIPERIDINE DERIVATIVES INHIBITING PRENYL TRANSFERASE PROTEINS AND METHODS FOR PREPARING SAME<br/>[FR] DERIVES D'AMINOPHENYLE PIPERAZINE OU D'AMINO PHENYLE PIPERIDINE INHIBITEURS DE PROTEINES PRENYL TRANSFERASE
  申请人：PF MEDICAMENT

  公开号：WO2002030927A1

  公开（公告）日：2002-04-18

  L'invention concerne des composés répondant à la formule générale (I), dans laquelle notamment : W représente : hydrogène, COR6, CSR6, SO2R6, CO(CH2)nR6, (CH2)nR7 ; X représente : CH ou N ; Y représente : (CH2)n, CO, CH2CO, CH=CHCO, CH2CH2CO ; Z représente un hétérocycle. Quand Z = pyridine alors Y est différent de CO. R1 représente : Hydrogène, C1-C6 alkyle, halogène, OCH3, CF3. R2 et R3, identiques ou différents représentent : Hydrogène, C1-C6 alkyle. R4 représente : a) Hydrogène ; b) C1-C6 alkyle ; c) un aryle ; d) un hétérocycle. R5 représente : Hydrogène, COR7, SO2R7, CO(CH2)nSR7, CO(CH2)nOR7, CONR7R8, CSNR7R8, CO(CH2)mCOR7. R6 représente : a) un phényle ou un naphtyle ; b) un C1-C6 alkyle, un cycloalkyle ; c) un hétérocycle ; d) NR7R8. R7 et R8, identiques ou différents, représentent : a) Hydrogène ; C1-C15 alkyle ; b) un hétérocycle ; c) un aryle. n représente : 0 à 10. m représente : 2 à 10 ; à la condition toutefois que, lorsque Z représente un groupement quinazoline ou benzimidazole, alors R5 est différent de CH2Ph ou Méthyl et n est différent de zéro.