4-(4-Nitro-phenyl)-piperazine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester | 412331-97-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 4-(4-Nitro-phenyl)-piperazine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester
• 英文别名: 9H-fluoren-9-ylmethyl 4-(4-nitrophenyl)piperazine-1-carboxylate
• CAS: 412331-97-6
• 化学式: C₂₅H₂₃N₃O₄
• 分子量: 429.475
• InChiKey: WEMXLIKDPSFXJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  78.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-Nitro-phenyl)-piperazine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 4-{4-[benzenesulfonyl-(3H-imidazol-4-ylmethyl)amino]phenyl}-1-piperazinecarbothioic acid cyclohexylamide
  参考文献：
  名称：

  Synthesis and evaluation of a novel series of farnesyl protein transferase inhibitors as non-peptidic CAAX tetrapeptide analogues

  摘要：

  A novel series of compounds, derived from 4-amino-phenyl piperazine, has been designed to selectively inhibit farnesyl protein transferase (FPTase) as CAAX tetrapeptide analogues. Certain of these compounds were shown to possess low nanomolar inhibitory activity both against the isolated enzyme and in cultured cells. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00170-7
• 作为产物：
  描述：

  1-(4-硝基苯基)哌嗪 、 9-芴甲基-N-琥珀酰亚胺基碳酸酯 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 4-(4-Nitro-phenyl)-piperazine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester
  参考文献：
  名称：

  Synthesis and evaluation of a novel series of farnesyl protein transferase inhibitors as non-peptidic CAAX tetrapeptide analogues

  摘要：

  A novel series of compounds, derived from 4-amino-phenyl piperazine, has been designed to selectively inhibit farnesyl protein transferase (FPTase) as CAAX tetrapeptide analogues. Certain of these compounds were shown to possess low nanomolar inhibitory activity both against the isolated enzyme and in cultured cells. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00170-7

文献信息

• Synthesis and evaluation of 5,7-dichloro-4-(3-{4-[4-(2-[¹⁸F]fluoroethyl)-piperazin-1-yl]-phenyl}-ureido)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid as a potential NMDA ligand to study glutamatergic neurotransmission in vivo
  作者：Markus Piel、Ralf Schirrmacher、Sabine Höhnemann、Wilhelm Hamkens、Beate Kohl、Michaela Jansen、Ullrich Schmitt、Hartmut Lüddens、Gerd Dannhardt、Frank Rösch

  DOI：10.1002/jlcr.682

  日期：2003.6

  The neurotransmitter glutamate is thought to be crucially involved in a huge number of neurological and psychiatric disorders, such as Morbus Parkinson, Alzheimer's disease and schizophrenia. Aiming at an improved diagnostic tool for PET a new [18F]fluorine labelled NMDA receptor ligand was developed that may potentially allow the in vivo visualization of glutama-tergic neurotransmission. The 19F-analogue trans-5,7-dichloro-4-(3-4-[4-(2-fluoroethyl)-piperazin-1-yl]-phenyl}-ureido)-1,2,3,4-tetrahydro quinoline-2-carboxylic acid was synthesised to determine the binding affinity, lipophilicity and biodistribution of the ligand. This substance exhibits a Ki of 12 nM for the glycine binding site using [3H]MDL-105,519 assays on pig cortical membranes. A logD of 1.3 was determined for this compound according to the OECD guidelines employing the HPLC method. Radiosynthesis of this ligand was achieved by labelling the precursor trans-5,7-dichloro-4-[3-(4-piperazin-1-yl-phenyl)-ureido]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid methyl ester with 2-[18F]fluoroethyltosylate and subsequent cleaving of the methyl ester moiety, resulting in an overall decay corrected yield of 35% of the final product trans-5,7-dichloro-4-(3-4-[4-(2-[18F]fluoroethyl)-piperazin-1-yl]-phenyl}-ureido)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid. The biodistribution kinetics of this compound were determined with Sprague Dawley rats ex vivo for brain, liver, kidney, and bone. The ligand showed a maximum brain uptake 30 min.p.i. of about 0.1% ID/g. Copyright © 2003 John Wiley & Sons, Ltd.

  神经递质谷氨酸被认为与许多神经系统和精神疾病密切相关，如帕金森病、阿尔茨海默病和精神分裂症。为了改进PET诊断工具，研究人员开发了一种新的氟-18标记的NMDA受体配体，这可能允许体内可视化谷氨酸能神经传递。 研究人员合成了19F类似物 trans-5,7-二氯-4-(3-4-[4-(2-氟乙基)-哌嗪-1-基]-苯基}-脲基)-1,2,3,4-四氢喹啉-2-羧酸，以确定配体的结合亲和力、亲脂性和生物分布。使用猪皮质膜上的[3H]MDL-105,519测定，该物质对甘氨酸结合位点的Ki值为12 nM。根据OECD指南使用HPLC方法测定，该化合物的logD值为1.3。 该配体的放射性合成是通过用2-[18F]氟乙基托烷磺酸酯标记前体 trans-5,7-二氯-4-[3-(4-哌嗪-1-基-苯基)-脲基]-1,2,3,4-四氢喹啉-2-羧酸甲酯，随后裂解甲酯基团实现的，最终产物的衰变校正产率为35%。 在Sprague Dawley大鼠上对脑、肝、肾和骨进行了该化合物的生物分布动力学体外测定。该配体在注射后30分钟显示最大脑摄取量约为0.1% ID/g。 Copyright © 2003 John Wiley & Sons, Ltd.
• 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
• [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.
• Synthesis and evaluation of a novel series of farnesyl protein transferase inhibitors as non-peptidic CAAX tetrapeptide analogues
  作者：Michel Perez、Catherine Maraval、Stephan Dumond、Marie Lamothe、Philippe Schambel、Chantal Etiévant、Bridget Hill

  DOI：10.1016/s0960-894x(03)00170-7

  日期：2003.4

  A novel series of compounds, derived from 4-amino-phenyl piperazine, has been designed to selectively inhibit farnesyl protein transferase (FPTase) as CAAX tetrapeptide analogues. Certain of these compounds were shown to possess low nanomolar inhibitory activity both against the isolated enzyme and in cultured cells. (C) 2003 Elsevier Science Ltd. All rights reserved.